Chemistry of Secondary Metabolites and Their Antimicrobial Activity in the Drug Development Process: a Review of the Genus Anogeissus
Chemistry of secondary metabolites and antimicrobial activity in the drug development process 1 Review Article
Chemistry of secondary metabolites and their antimicrobial activity in the drug development process: a review of the Genus Anogeissus
A. Mann1, J.O. Amupitan2, A.O. Oyewale2, J.I. Okogun3 and K. Ibrahim 4 1Department of Science Laboratory Technology, The Federal Polytechnic, Bida, P.M.B. 55, Bida, Niger State, Nigeria 2Department of Chemistry, Ahmadu Bello University Zaria, Kaduna State, Nigeria 3Department of Medicinal Plant Research and Traditional Medicine, National Institute for Pharmaceutical Research and Development (NIPRD), P.M.B. 21, Garki – Abuja, Nigeria 4Department of Microbiology and Biotechnology, National Institute for Pharmaceutical Research and Development (NIPRD), P.M.B.21, Garki – Abuja, Nigeria
ABSTRACT
The significance of secondary metabolites as antimicrobial agents and its chemistry in the drug development process is reviewed. The genus Anogeissus (Combretaceae) is widely distributed in most tropical and subtropical countries of the world. Anogeissus is a genus of trees, shrubs or small trees. The genus has eight species, five native to South Asia, two indigenous to the southern Arabian Peninsula, and one native to Africa. Genus Anogeissus have long been used in traditional medicine to treat a broad spectrum of disorders. Chemical constituents isolated from Genus Anogeissus so far include amino acids, terpenoids (and their glycoside derivatives); steroids; flavonoids and their glycosides; tannins and other phenolic compounds and lignan. The focus of this paper has been on the phytochemistry of the species of Anogeissus and with the bioactivities of their various metabolites and their general potential in drug development were reviewed. [Medicinal Plants 2009; 1(2) : 00-00].
Keywords : Anogeissus, Antimicrobial activity, Chemical constituents, Ethnobotanical uses, Drug development, Secondary metabolites, Pharmacological activity
INTRODUCTION extracts have been performed, many plants used in different traditional medicinal systems have never been In traditional medicine, plants are the major components evaluated for their antimicrobial effects. The major and it is used as such without isolating the active problem in investigations on the biological activities of ingredients in herbal preparations. Crude plant extracts plant extracts and phytomedicines lies in the fact that might be more important as drugs than the purified form a variety of plants may be used in a single traditional used in the western medicine, since plants contain medicine preparation, and in the possibility of synergistic numerous secondary metabolites, and pathogens in effects resulting from the interactions of the compounds nature interact with many chemicals simultaneously in the extract. This can even result in a loss of activity (Izhaki, 2002). Traditional plant remedies or as the extract is purified (Couzinier and Mamatas, 1986). phytomedicines include crude vegetable drugs (herbs) Eloff and McGaw (2006) pointed out that biologically as well as galenical preparations (extracts, fluids, active extracts can be extremely useful in their entirety, tinctures, infusions) prepared from them. Although a taking into account synergistic and other effects. A number of studies of the antimicrobial effects of plant standardized and formulated plant extracts as drugs might be the starting point in developing countries for a successful pharmaceutical industry to be able to Corresponding author : A. Mann compete with Western pharmaceutical companies. E-mail : [email protected]
Medicinal Plants, 1(2) July, 2009 2 Mann et al.
Natural products and their derivatives have historically use, random collection or a chemotaxonomic approach been invaluable as a source of therapeutic agents. Natural (Mann, 2007). Before beginning a phytochemical and product chemistry through systematic investigation, pharmacological investigation, a literature search should using chemical principles, helps to develop drugs for be performed on the genus or species in question. It is chemotherapy in modern medicine. It was predicted that possible to discover all the previous research which by 2005 more natural-based medicines would penetrate has been performed on the plant(s) selected for study the largely synthetic global pharmaceutical market by which is the focus of this type of review. Selection of as much as 30% (Wilkinson, 2000a). This is in-line with plants based on data from traditional medicine can also increased awareness and appreciation of plant-derived lead to the discovery of promising new molecules drugs and therapy in both the general public and (Hostettmann et al., 2000). Plants from tropical and scientific community. Pharmaceutical versions of herbal subtropical regions occur in abundance but, they have medicines are now being developed. This may lead to been little studied (Hostettmann et al., 2000). The genus an emergence of a whole new type of pharmaceutical Anogeissus represents an enormous reservoir of new drug (Wilkinson, 2000b). As a consequence, the market molecules with potential therapeutic activity which is for supply of high quality herbal extracts and supply of waiting to be discovered. raw materials will drastically increase. The herbal market is likely to grow from around $US5billion to at least Ethnobotanical uses and Pharmacological activity $US30billion as these medicines enter the $US100billion Anogeissus has been used in herbal medicine in many market for pharmaceuticals (Wilkinson, 2000a). Since the countries for several purposes especially in Africa and development of safe, effective and inexpensive drugs India where its species are widely distributed. It is a are on the top priority of the global drug development very large genus of Combretaceae family consisting of (Chattopadhyay, 2006), it is the aim of the present paper many species such as: Anogeissus acuminata (Synonym: to attract the attention of phytochemists, particularly A. pendula), Anogeissus bentii, Anogeissus dhofarica, those from the developing countries, to take the available Anogeissus latifolia, Anogeissus leiocarpus (Synonyms: opportunities in this genus Anogeissus by intensively A. leiocarpa or A. schimperi or Conocarpus leiocarpus), evaluating its potentials for the drug discovery and Anogeissus rotundifolia and Anogeissus sericea. The drug development. During the last two decades there most studied species are: A. acuminata, A. latifolia and has been an upsurge in the search for new plant-derived A. leiocarpus, thus the present review focus on these drugs containing medicinally useful alkaloids, species. Anogeissus acuminata var lanceolata (Roxburgh glycosides, polyphenolics, steroids, and terpenoid ex Candolle) Guillaum & Perr / Wallich ex CB Clarke is derivatives. The World Health Organization estimates one of the timber trees of Bangladesh. It is commonly that approximately 80% of the world’s population relies called Itchri and Yon. Due to the durability of its timbers, primarily on traditional medicines as sources for their it is used in the manufacturing of handle of tools and primary health care delivery (Farnsworth et al., 1985). Catamaran; which is a traditional fishing craft found Over 100 chemical substances that are considered to be along the Indian coast (Rao et al., 2006). It is used as important drugs are either currently in use or have been herbal drug for treating diarrhoea in India (Dash and widely used in one or more countries in the world have Padhy, 2006). The extract of its timber exhibited been derived from a little under 100 different plants leishmanicidal activity (Takahashi et al., 2004). (Fabricant and Farnsworth, 2001). Approximately 75% of these substances were discovered as a direct result of Anogeissus latifolia (Roxb. ex DC.) Wall. ex Guill. & chemical studies focused on the isolation of active Perr. is a perennial deciduous tree with common names substances from plants used in traditional medicine as axle-wood tree, Buttontree, dindiga-tree, ghattitree, (Cragg and Newman, 2001a,b). Secondary metabolites gum-ghatti, baklee, dhaura and Indian gum (Bhatt, 1987); isolated from medicinal plants can serve as precursors other local names are : Dhaura, Dhausa, Dhau, Dhawra, or models for the preparation of effective agents through Dhawa, Bakli, Dindal, Dinduga, Vellay naga, Chiriman. semi-synthesis or lead-based total synthesis. Anogeissus latifolia is one of the most useful trees in Constituents are often specific to a given botanical India (Firewood and Pak, 1997; Kala et al., 2004). A. family, to a genus or to a species. If a natural product latifolia leaves are fed to silkworms and contain large has interesting therapeutic properties, it may be possible amounts of tannin/dyestuff, and are used in India as to find analogous substances in species of the same such. The tree is the main source of commercial Indian genus or the same family. Natural products can be gum, known as ghatti gum, which is used for calico selected for biological screening based on ethnomedical printing among other uses. Ethnobotanically, the bark
Medicinal Plants, 1(2) July, 2009 Chemistry of secondary metabolites and antimicrobial activity in the drug development process 3 of Anogeissus latifolia has also been reported to be practitioners in Nigeria (Johnbull and Abdu, 2006; Mann, used in the treatment of various skin diseases such as 2007). The flower of the plant is also known to be fried, sores, boils and itching (Roy and Chaturvedi, 1986), ground and later infused in warm water as treatment wound (Dutta, 1941), snake and scorpion bites, stomach against tape worm. The root and stem of the plant have diseases (Jain, 1997; Jain and Tarafder, 1970), colic been used as chewing sticks for dental hygiene. The (Apparanantham and Chelladurai, 1986), cough (Balla et powdered bark is applied to wounds and ulcers, and an al., 1986), diarrhoea (Ramachandran and Nair, 1981) and aqueous extract of the bark is similarly used in Senegal gonorrhoea (Nadkarni, 1976); and the extract is recorded to treat diarrhoea. In Cote D’ivoire and in Burkina-Faso, as possessing demulcent and astringent properties the powdered bark with that of Terminalia sp are applied (Nadkarni, 1976). Several pharmacological activities of to the gum for toothache and a decoction from the bark A. latifolia have been reported to possess antibacterial and the twigs used to clean sores and treat syphilis. activity and antioxidant potential (Govindarajan et al., Root bark is also used as stimulant and aphrodisiac. In 2004a,b, 2005); antifungal activity (Chaturvedi et al., some regions of Upper Guinea, the bark is used as a 1987); and antiulcer potential and antimicrobial activities febrifuge in hot lotions and infusions and also for (Govindarajan et al., 2006). Rahman et al. (2007) screened leprosy cure in Burkina-Faso. The leaves serve as a the ethyl acetate and methanol extracts of A. latifolia fodder to livestock (Burkill, 1985). The powdered bark and that it exhibited significant inhibitory activity of has also been mixed with green clay and applied as an microbial growth, while the ethyl acetate extract unusual face mask for serious Acne vulgaris and demonstrated significant cytotoxicity to brine shrimp blackhead skin with good results (Dalziel, 1956). In with LC50 at 0.50 µg/ml. It was observed that the results Northern Nigeria, the gum is eaten by the Hausas, where of antimicrobial and cytotoxicity screenings are it is regarded by some as the best gum for chewing. consistent with the folk uses of A. latifolia by the local Apart from ethnobotanical uses, the most common use people (Rahman et al., 2007). of this plant is in the production of glue. The stem exudates of A. schimperi (Aspinall and Chaudhari, 1961) Anogeissus leiocarpus is a graceful tree of Africa, and A. leiocarpus (Aspinall and Chaudhari, 1975), and commonly known as “African birch” because of the A. latifolia (Nadkarni, 1976) are the three species most silvery cast of the foliage like the temperate birch. It commonly used as gum. They are also source of sugars, extends from the Sahel to forest zones and Senegal to for example, 1-arabinose was isolated in commercial Sudan and Ethiopia with savanna regions as its habitats quantity from stem exudates of A. latifolia (Ingle et al., (Burkill, 1985). In Nigeria, A. leiocarpus is popularly 1985). known with these local names: Hausa: marike, marke; Nupe: shici; Fulfulde: galaldi, kojoli, Yoruba: ayin, pako Chemistry of secondary metabolites and their ayin, orin-odan, Igbo: atara. In Nigeria, A. leiocarpus antimicrobial activities is used as a remedy for many ailments of livestock and man, which include helminthosis, schistosomiasis, Plants are inventive chemists (Mann, 2007). They have leprosy, diarrhoea and psoriasis (Burkill, 1985; Ibrahim an almost limitless ability to synthesize chemical et al., 1985). The application of powdered bark to substances. Some of the chemical substances are wounds, sores, boils, cysts, and diabetic ulcers gives nutritious, poisonous, hallucinogenic or therapeutic in good results. Among the Hausas in the northern nature. Most are secondary metabolites which often savannah region of Nigeria, the leaves of A. leiocarpus serve as plant defense mechanisms against predation is fed as a mixture of forage leaves to cattle, sheep and by microorganisms, insects and herbivores. Many among goats suffering from influenza nasal or mucus infections. these type of compounds are responsible for plant Decoction of the leaves with red potash is widely used flavour e.g. terpenoids (Cowan, 1999). Though some of in oral application as cough mixtures. Its combination these compounds may not have any discernible with spider’s nut from Cassia singeana tree is orally physiological roles in the plants in which they occur, taken to cure pulmonary tuberculosis. It has also been many of them have significant biological effects on used to treat trypanosomiasis in Kaduna state of Nigeria animals. However, it is generally accepted that they (Atawodi et al., 2002) and its in vitro trypanocidal play an essential role in plant physiology such as plant effects has been evaluated (Atawodi et al., 2003). A. growth, development and reproduction, and in the leiocarpus is ethnobotanically known to be the most interaction between the plant and its environment active ingredient responsible for chemotherapy of (Whiting, 2001). In fact, they are responsible for the tuberculosis as claimed by indigenous medical therapeutic effect of plants. Some of these metabolites have been isolated and found to have antimicrobial
Medicinal Plants, 1(2) July, 2009 4 Mann et al. properties in vitro (Van Etten et al., 1994). Such chemical state, Nigeria (Abdullahi et al., 2003). Johnbull and Abdu substances with antimicrobial activity are grouped as (2006) carried out screening of crude extracts of A. phenols, acids, alkaloids, flavonoids, terpenoids and leiocarpus and found that the efficacy compares very polyacetylenes and phenylheptatriyene (Oliver-Bever, well with the Huperzine A. A. leiocarpus was found to 1983). Most antimicrobial secondary metabolites have be most active with the MICs ranging from 0.25 mg/ml relatively broad spectrum of activity. Several to 4 mg/ml amongst the five species of Combretaceae antimicrobial studies have been conducted on the grown in Togo that were investigated for their antifungal extracts of medicinal plants worldwide showing herbal activity (Batawila et al., 2005). In addition, Vonthron- medicine as a source of chemotherapeutic agents with Senecheau et al. (2003) and Taiwo et al. (1999) have significant potency. Plant secondary metabolites can demonstrated that A. leiocarpus has shown activity function as antimicrobial agents, insecticides, pollinator against a variety of bacteria, Methicillin-Resistant attractants, growth regulators, feeding deterrents, Staphylococcus aureus 595445. In another investigation, signalling compounds, and as allephatic agents that the results of in vitro antiplasmodial activity and influence competition among plant species. Recognition cytotoxicity of four Ivorian medicinal plant species of the biological properties and functions of the showed that methylene chloride extract of A. leiocarpus countless number of natural products have encouraged was the most active at concentration of 3.8 µg/ml at the awareness in this field of metabolites as possible IC50 (Vonthron-Senecheau et al., 2003). Several sources for new drugs. Apart from their use as antimicrobial activities of various extracts of A. preservatives, flavourants and pigments, plant secondary leiocarpus from different parts against pathogens such metabolites have featured extensively for their use in as Streptococcus mutans, Pseudomonas aeruginosa, medicine. Many of the active principles of folklore Klebsiella pneumoniae, Salmonella typhimurum and medicine have now been identified. Globally, medicinal Enterococcus faecium demonstrated various degrees of plants are still a part of the daily life of many people activity (Ibrahim et al., 2005; Kudi et al., 1999; Mann et benefiting them from their use (Mann, 2007). al., 2007a,b; 2008a,b,c; Taiwo et al., 1999). Studies have shown anti-microbial and anti-fungal activity based on Many pharmacological activities of A. leiocarpus the composition comprising of biomass extracts isolated have been reported to possess antimicrobial activities from Zanthoxylum gillettii and Anogeissus leiocarpus (Adeleye et al., 2003; Bhatt and Saxena, 1979; Machido in combination with citrus juice to treat symptoms and and Ado, 1999; Ibrahim et al., 1995; 2005; Mann et al., infections associated with HIV by operating in the body 2007c; 2008a,b,c; Ndukwe et al., 2005; Sani et al., 2007; to decrease viral load, increase CD4 count, increase Sanogo et al., 1997; Taiwo et al., 1999; Uba et al., weight, and decrease the incidence and severity of 2003). Preliminary phytochemical screening of extracts symptoms including diarrhea, fatigue, anorexia, cough from A. leiocarpus indicated presence of anthraquinone, and fever (US Patent, 2004). The antitrypanosomal carbohydrate, saponins, steroids, tannin, and terpenoids activity of methanolic extracts of Anogeissus leiocarpus (Adeleye et al., 2003; Mann et al., 2007b,c; 2008b,c). and Terminalia avicennioides were evaluated in vitro One distinct feature of this genus is the absence of against four strains of Trypanosoma species with (MIC) alkaloids (Adeleye et al., 2003; Mann et al., 2007b,c; value range of 12.5–50 mg/ml (Shuaibu et al., 2008). 2008b,c). In Nigeria and Ghana, the roots of the plant Furthermore, the successive fractionation of the two are used as a chewing stick, but the antibiotic activity plant extracts in water, butanol and ethyl acetate gave test conducted on the root did not give any significant a range of improved activity (Shuaibu et al., 2008). results (Olabanji et al., 1996). However, the extract of A. Some toxic effects of the aqueous leaf extract of leiocarpus was found to show an impressive activity Anogeissus leiocarpus was evaluated in rats using against the broad spectrum of organisms used in the changes in haematological and biochemical parameters test (Rotimi et al., 1988). Even though, Rotimi et al. as well as body weight changes. The results suggested (1988) found that the extracts of A. leiocarpus was toxic that the aqueous leaf extract of A. leiocarpus could in mice. In another development, aqueous extract of A. affect feed intake and utilization and also elicit some leiocarpus which is used as a local drug in Sudan; the changes in biochemical parameters (Agaie et al., 2007). phytotherapy experiments showed a mild anthelmintic Recently an investigation of the antifungal activity action on free living Rhabdiud nematode (Ibrahim, 1992). revealed that the hydroethanol extracts of Terminalia A. leiocarpus aqueous extracts are among the glaucescens Planch. ex Benth. (L.) and Anogeissus preparations used in the ethnoveterinary practices leiocarpus (D.C.) Guill. et Perr. (L.) appeared to be the adopted for the treatment of poultry diseases in Bauchi most active, with IC50 values ranging from 0.25 to 4 mg/
Medicinal Plants, 1(2) July, 2009 Chemistry of secondary metabolites and antimicrobial activity in the drug development process 5 ml (Okigbo and Mmeka, 2006). In a preliminary evaluation can make the isolation and identification of the of antimicrobial activity of the plants, A. leiocarpus substances present in the plant very laborious. Different was found to inhibit the growth of all the test environmental conditions can also affect the chemical microorganisms (Kubmarawa et al., 2007). During in vitro constitution of the plants. The choice of solvent in the evaluation of the selected plants in ethnopharmacological isolation process is also very crucial, because the use survey of antiparasitic medicinal plants used in Ivory of ethanol or methanol may lead to the production of Coast, A. leiocarpus and T. glaucescens were strongly artefacts, e.g. ethyl gallates or methyl gallates, during active against Plasmodium falciparum (Okpekon et al., the extraction process (Calixto et al., 1998). The 2005). A. leiocarpus was one of the plants found to compounds with bioactivity are not restricted to a possess antifungal and antioxidant activities out of particular chemical group. They are, however, mostly fourteen plants used in the treatment of sexually amino acids, terpenes, flavonoids, alkaloids, tannins, transmitted infections in Mali (Sanogo, 2005). Dakaline steroids or their glycosides. Branched chains, uronic is obtained from A. leiocarpus bark and the active acids moiety and pyran rings are fairly common in the ingredient demonstrates striking anti-ageing properties diverse structures including polyhydroxyl and acidic and has a triple action against the signs of skin ageing. functional groups. Most of these agents are acids, and/ In addition, its bark also produces Anogelline, a or triterpenes. This would suggest a pharmacodynamics substance used in cosmetics. The likely mechanism is based essentially on the presence of at least one by incorporation of L-ascorbic acid inside human carboxylic group, and a structure-activity relationship fibroblasts (women of 40 years old, abdomen skin) has based on the presence of some terpene and carboxylic been treated with methanol extract of the bark of A. acid moieties. A number of compounds have been leiocarpus at different concentrations (2.5 and 5 µL/mL) isolated from plants in this genus. They can be classified and the extract increases the bioavailability of the as flavonoids, tannins, terpenoids and miscellaneous ascorbic acid inside the fibroblast. Among the wide substances, an account of which is given in tables range of plant species belonging to the genus 1-4. Anogeissus, three species, A. acuminata, A. latifolia and A. leiocarpus are the phytochemically and 1. Distribution of flavonoids and their glycosides in biologically investigated (Adigun et al., 2001; Chaabi et Anogeissus species al., 2006; Lin et al., 1991; Reddy et al., 1965, 1974; Flavonoids are a large group of low molecular weight Rimando et al., 1994b). polyphenolics found in virtually all vascular plants. Chemistry of secondary metabolites Flavonoids are constitutive compounds but are also produced by plants in response to microbial infection The building blocks for secondary metabolites are (Dixon et al., 1983). Their activity has been attributed derived from primary metabolites. With only a limited to their ability to complex with extracellular and soluble number of building blocks, a vast array of secondary proteins and to complex with bacterial cell walls (Cowan, metabolites can be produced. The most important 1999). Flavonoids have been found to show in vitro elements employed in the biosynthesis of secondary antimicrobial activity against a wide range of metabolites are derived from the intermediates acetyl microorganisms, some showing potent activity against coenzyme A, shikimic acid, mevalonic acid, and 1- MRSA (Iinuma et al., 1994). Flavonoid compounds deoxyxylulose-5-phosphate. These are employed exhibit inhibitory effects again multiple viruses; e.g. respectively in the acetate, shikimate, mevalonate, and chrysin is a flavonoid compound active against HIV. deoxyxylulose phosphate pathways. Secondary Lipophilic flavonoids may also disrupt microbial metabolites can be synthesized by the combination of membranes (Tsuchiya et al., 1996). The low toxic several elements of the same type, or by using a mixture potential of flavonoids makes them ideal as antimicrobial of different types. Many secondary metabolites can also medicines (Cowan, 1999). Flavonoids have a range of contain one or more sugar molecules, either simple biological effects on mammalian cell systems, in vitro primary metabolites (such as glucose) or substantially as well as in vivo. Flavonoids have been shown to modified and unusual sugars. possess antiviral and endocrine effects, activity on mammalian enzymes, effects on the modulation of Chemical constituents of Anogeissus species immune and inflammatory cell functions, effects on smooth muscles, and on lipid peroxidation and oxyradical The complexity of the mixture of compounds and the production (Harborne, 1994). Over production of oxidants presence of several compounds in small concentrations so-called free radicals cause damage to the body cells
Medicinal Plants, 1(2) July, 2009 6 Mann et al. and even alter their genetic code. Oxidation may octacosane), triglyceride and cholesterol from the specifically contribute to wrinkling by activating the petroleum spirit extract. specific metalloproteinases that degrade connective tissue. Increase of metalloproteinases that degrade 2. Distribution of terpenoids and their glycosides in collagen leading to an uneven formation of disorganized Anogeissus species collagen fibres. Current medicinal knowledge of the Essential oils are highly enriched in compounds based activity of plant phenolics indicates that useful drugs on an isoprene structure. They are called terpenes, their may be developed from them in the future, or that they general chemical structure is C H , and they occur as could be used as templates for further research and 10 16 diterpenes, triterpenes, and tetraterpenes (C , C , and development. 20 30 C40), as well as hemiterpenes (C5) and sesquiterpenes The bark of A. latifolia was first examined by Reddy (C15). When the compounds contain additional elements, et al. (1965), who isolated ellagic acid [1] and (+)- usually oxygen, they are termed terpenoids (Cowan, leucocyanidin [2]. In addition, the isolation of 3, 4, 3’- 1999). Terpenoids are synthesized from acetate units, tri-O-methylellagic acid [3] and 3, 4, 3’-tri-O- and as such share their origins with fatty acids. methylflavellagic acid [4], were reported by Reddy et al. Terpenoids differ from fatty acids in that they contain (1965, 1974) from the bark and wood extractives of A. extensive branching and are cyclized. Examples of latifolia. common terpenoids are menthol and camphor (monoterpenes) and farnesol and artemisin Later, ellagic acid and two new glycosides of ellagic (sesquiterpenes). Terpenes and terpenoids are active and flavellagic acids namely, 3, 3’-di-O-methyl ellagic against bacteria, fungi, viruses, and protozoa (Amaral et acid-4-β-xyloside [5], and 3, 4, 3’-tri-O-methylflavellagic al., 1998; Himejima et al., 1992; Mendoza et al., 1997). acid-4-β-D-glucoside [6] were reported by Deshpande The triterpenoid betulinic acid is just one example of et al. (1976). The isomer of 3, 3’-4’-tri-O-methylflavellagic several terpenoids, which have been shown to inhibit acid [7], was also isolated from the aqueous extract of HIV. The mechanism of action of terpenes on microbes the bark of A. schimperii (syn A. leiocarpus), together is not yet fully understood, but it is speculated to with the aglycone of 3, 3’-di-O-methylellagic acid[8] involve membrane disruption by the lipophilic (Nduji and Okwute, 1988). The structure of flavellagic compounds. Accordingly, Mendoza et al. (1997) found and ellagic acids are similar to those of flavone and it that addition of a methyl group on kaurene diterpenoids is interesting to note that Reddy et al. (1965) also drastically reduced their antimicrobial activity. When reported the isolation of leucocyanidin [1] from the bark different series of terpenoids were investigated for their of A. latifolia. The chloroform extract from the water antimicrobial effects it was found that the more lipophilic soluble portion of defatted root of A. latifolia was found compounds were significantly more antibacterial than to contain the flavenoidal glycoside,quercetin-3-O-β-D- their more polar analogues (Cantrell et al., 2001). galactopyranosyl-(1,4)-O-α-L-rhamnopyranoside [9] (Chaturvedi and Saxena, 1985). Fractionation of the ethanol bark crude extracts of A. leiocarpus gave two saponins of oleane type (Chaabi Adigun et al. (2000) isolated 3, 4, 3’-tri-O- et al., 2006). They were identified as olean-12-en-28-oic methylflavellagic acid and its glucoside from A. acid 2α, 3β, 19α, 23,24-pentahydroxy-β-D-glucopyranosyl leiocarpus. Antimicrobial effect of the glucoside ester (trachelosperoside E1) (11) and olean-12-en-28-oic obtained from A. leiocarpus on S. aureus, E. coli, Ps. acid 2α,3β,19α,23-tetrahydroxy-β-D-glucopyranosyl ester aeruginosa and C. albicans show that it possesses (arjunglucoside I) (10) (Chaabi et al., 2006). A growth inhibitory effect at various concentrations comparison of their antiprotozoal activity shows that (Adigun et al., 2000). The preliminary antimicrobial (10) has a good antitrypanosomal activity screening of the petroleum spirit extract of A. leiocarpus (IC50=1.24µM), without significant cytotoxicity (SI >100) indicates inhibitory effect against B. subtilis and Ps. (Chaabi et al., 2006). Chaabi et al. (2008) also isolated aeruginosa (Adigun et al., 2001). They also reported a number of triterpenes and polyphenols from A. the isolation of saturated carboxylic acids (tetradecanoic, leiocarpus. 3-β-hydroxy-28-acetyltaraxaren and β- hexadecanoic and octadecanoic acid), unsaturated acids sitosterol were isolated from an ethyl acetate extract of (linoleic acid and oleic acid) together with their esters the stem bark of A. latifolia. However, the activity tests 11, 14-eiocosadiennic acid methyl ester and its isomer, were not done on isolated compounds (Rahman et al., as well as long-chain hydrocarbons (tricosyne and 2007)
Medicinal Plants, 1(2) July, 2009 Chemistry of secondary metabolites and antimicrobial activity in the drug development process 7
Table 1 : Distribution of flavonoids and their glycosides in Anogeissus species
Plant and Chemical compounds Category Plant Reference part
Anogeissus latifolia (Roxb. ex. DC.) Wall. ex Guill. & Perr.
Ellagic acid [1] Flavanone Bark Reddy et al., 1974
Leucocyanidin [2] Flavanone Bark Reddy et al., 1974
3, 4, 3'-Tri-O-methylellagic acid [3] Flavanone Bark Reddy et al., 1974
3, 4, 3'-Tri-O-methylflavellagic acid [4] Flavanone Wood Reddy et al., 1974
Medicinal Plants, 1(2) July, 2009 8 Mann et al.
Table 1 : Continued ......
Plant and Chemical compounds Category Plant Reference part
Quercetin-3-O-β-d-galactopyranosyl-(1,4)-O-1- Flavenoidal glycoside Wood Chaturvedi and Saxena, 1985 rhamnopyranoside [5]
Anogeissus leiocarpus (DC.) Guill. & Perr.
3, 4, 3'-Tri-O-methylflavellagic acid-4'-β- Flavanone glycoside Stem bark Adigun et al., 2000 D-glucoside [6]
Anogeissus schimperi Hochst. ex. Hutch. & Dalz.
3, 3'-Di-O-methylellagic acid [7] Flavanone Stem bark Nduji and Okwute, 1988
Medicinal Plants, 1(2) July, 2009 Chemistry of secondary metabolites and antimicrobial activity in the drug development process 9
Table 1 : Continued ......
Plant and Chemical compounds Category Plant Reference part
3, 3'-Di-O-methylellagic acid-4'-β-D- Flavanone glycoside Stem bark Deshpande et al., 1976 xyloside [8]
3, 3', 4'-Tri-O-methylflavellagic acid [9] Flavanone Stem bark Nduji and Okwute, 1988
3. Distribution of tannins and other phenolic biological activities, e.g. simple benzenoid and compounds in Anogeissus species flavonoids, are biosynthesized via shikimic acid and acylpolymalonate pathway. Several thousand phenolic compounds occur widely throughout the plant kingdom (Harborne, 1995; Haslam, Tannin is a general descriptive name for a group of 1998). Natural phenolic acids are widely represented in polymeric phenolic compounds capable of tanning fruits, although their distribution may vary considerably leather or precipitating gelatin from solution, a property according to species and physiological stage (Haslam, known as astringency. They are found in almost every 1998). Phenolic acids are of great interest to man because plant part. They are divided into two groups, namely they contribute to the sensory and nutritional qualities. hydrolysable and proanthocyanidins (condensed Natural phenolic compounds make a considerable tannins) (Schultz, 1988). Hydrolysable tannins (e.g. contribution to the nutritional quality of fruits and fruit pentagalloylglucose) are based on gallic acid and ellagic products, which play an important role in the daily diet acid usually as multiple esters with D-glucose; while (Whiting, 2001). Most natural antioxidants possess a the more numerous condensed tannins (e.g. procyanidin polyphenolic structure (Harborne, 1994; Haslam, 1998). B-2) are derived from flavonoid monomers (Haslam, Phenolic acids can act as endogenous precursors for 1998). Tannins have received attention in recent years many of the other phenolic molecules found in plants. due to their claimed ability to cure a variety of diseases A large number of phenols which possess distinct (Serafini et al., 1994). Many human physiological
Medicinal Plants, 1(2) July, 2009 10 Mann et al.
Table 2 : Distribution of terpenoids and their glycosides in Anogeissus species
Plant and Chemical compounds Category Plant part Reference
Anogeissus leiocarpus (DC.) Guill. & Perr.
Olean-12-en-28-oic acid 2α, 3β, 19α, Saponin Bark Chaabi et al., 2006 23-tetrahydroxy-β-D-gluco pyranosyl ester (Oleanane-type) (Arjunglucoside I) [10]
Olean-12-en-28-oic cid 2α, 3β, 19α, 23, Saponin Bark Chaabi et al., 2006 24-pentahydroxy-β-D-gluco pyranosyl ester (Oleanane-type) (Trachelosperoside E1) [11]
activities, such as stimulation of phagocytic cells, host- 1996). Tannins have also been found to induce changes mediated tumour activity, and a wide range of in the morphology of several species of ruminal bacteria antiinfective actions, have been assigned to tannins (Jones et al., 1994). Due to their ability to bind to (Haslam, 1996). One of their molecular actions is to proteins and metals, tannins also inhibit the growth of complex with proteins through non-specific forces such microorganisms through substrate and metal ion as hydrogen bonding and hydrophobic effects, as well deprivation (Scalbert, 1991). Hydrolysable and as by covalent bond formation. Thus, their mode of condensed tannins have been found to possess similar antimicrobial action may be related to their ability to antifungal and antibacterial potency, but the inactivate microbial adhesins, enzymes, cell envelope hydrolysable tannins were found to be more effective transport proteins (Cowan, 1999). Tannins have the against yeasts (Cowan, 1999). Some research has been ability to complex with proteins through non-specific performed on the relationship between tannin structure forces such as hydrogen bonding and hydrophobic and antimicrobial activity. The presence of a effects and also through covalent binding (Stern et al., hexahydroxydiphenoyl moiety or its oxidatively modified
Medicinal Plants, 1(2) July, 2009 Chemistry of secondary metabolites and antimicrobial activity in the drug development process 11
Table 3 : Distribution of tannins and other phenolic compounds in Anogeissus species
Plant and Chemical compounds Category Plant Reference part
Anogeissus acuminata (DC.) Guill. & Perr. R1 R2 R3 H H H Acutissimin A [12] Ellagitannin glycosides Bark Lin et al., 1991 H HHDP Acutissimin C [13] Ellagitannin glycosides Bark Lin et al., 1991 OH HHDP Eugenigradin [14] Ellagitannin glycosides Bark Lin et al., 1991
Anogeissinin [15] Ellagitannin glycosides Bark Lin et al., 1991
Medicinal Plants, 1(2) July, 2009 12 Mann et al.
Table 3 : Continued ......
Plant and Chemical compounds Category Plant Reference part
R---H, Anogeissusin A [16] Ellagitannin glycosides Bark Lin et al., 1991
R---OH, Anogeissusin B [17] Ellagitannin glycosides Bark Lin et al., 1991
R1 R2 R3 R4
OHHHHCastalin [18] Ellagitannin glycosides
OHH HHDP Castalagin [19] Ellagitannin glycosides Bark Lin et al., 1991
H CO2H HHDP Vescalagin carboxylic acid [20] Ellagitannin glycosides Bark Lin et al., 1991
Medicinal Plants, 1(2) July, 2009 Chemistry of secondary metabolites and antimicrobial activity in the drug development process 13
Table 3 : Continued ......
Plant and Chemical compounds Category Plant Reference part
Castamollilin [21] Ellagitannin glycosides Bark Lin et al., 1991
Grandinin [22] Ellagitannin glycosides Bark Lin et al., 1991
Medicinal Plants, 1(2) July, 2009 14 Mann et al. entities was an important feature for the anticryptococcal chromatography isolated three novel complex tannins activity of the ellagitannin such as corilagin (Latté and (flavano-ellagitannins), anogeissinin [15] having two C- Kolodziej, 2000). The pattern of B-ring hydroxylation of glycosidic ellagitannin (vescalagin) moieties connected monomeric flavonols in condensed tannins has been to the C-6 and C-8 positions in the (-)-catechin moiety), shown to affect the level of growth inhibition of and anogeissusins A [16] and B [17] (both with Clostridium botulinum (Hara and Watanabe, 1989), structures in which the dimeric C-glycosidic ellagitannin, Proteus vulgaris and Staphylococcus (Mori et al., 1987), castamollinin [21] is attached to the C-8 position of the and in all cases gallocatechins were more effective (-)-catechin and (-)-gallocatechin moieties). Eight known inhibitors than their catechin counterparts. The toxicity C-glycosidic hydrolysable tannins namely, acutissimin of tannins and lower molecular weight phenols has been A [12], acutissimin C [13], eugenigradin [14], castalin related to their oxidation state; catechin was found to [18], castalagin [19], vescalagin carboxylic acid [20], be devoid of any toxicity against methanogenic bacteria, castamollinin [21] and grandinin [22], were also isolated whereas if oxidized it strongly reduced methane from the bark of this plant. They were identified by production (Field et al., 1989). Natural phenolic direct comparisons of their physical and spectral data compounds also play a key role in antioxidative defence with those of authentic samples (Lin et al., 1991). mechanisms in biological systems and they may have Anolignan A isolated from Anogeissus acuminata inhibitory effects on mutagenesis and carcinogenesis. exhibited HIV-1 reverse transcriptase at 60.4 µg ml-1
Attention has now been turned to plant phenols because with IC50 (Chattopadhyay and Naik, 2006). the use of synthetic antioxidants has been falling off due to their suspected action as cancer promoters (Ho, 4. Distribution of miscellaneous compounds in 1992a). Caffeic acid, Gallic acid and gallic acid derivatives Anogeissus species (methyl-, lauryl and propylgallates) show strong Lignans are cinnamic acid derivatives. Lignans and antioxidant properties and act as free radical acceptors stilbenoids are compounds that are biogenetically (Bouchet et al., 1998; Ho, 1992b). They are widely used related, and they have generated immense interest as food additives to protect lipid structures. because of their biological potency and structural Nevertheless, phenols have pro-oxidant effects, i.e. it simplicity. A number of lignans have been shown to cause tissue damage by producing reactive oxygen possess antiviral activities (Charlton, 1998). species (ROS), and their consumption should be with Dibenzylbutadiene lignans, Anolignan A, 2-(2’-4’- caution (Aruoma et al., 1993). dihydroxybenyl)-3-(3’-4’-methylenedioxy-benzyl) 1, 3- Several of the virucidal plant compounds are tannins butadiene [23], and Anolignan B, 2, 3-bis–(4- or related phenolic substances, which are often hydroxybenzyl butadiene [24] were isolated from responsible for the virucidal effects (Whiting, 2001). In Anogeissus acuminata. Both compounds show HIV–1 general, polyphenols act by associating with proteins reverse transcriptase inhibitory activity individually and of viral particles and/or host cell surfaces, resulting in in combination through a bioassay-directed fractionation reduction or prevention of viral adsorption. procedure. A third new compound, Anolignan C, 2, 3- Proanthocyanidins and other tannins facilitate wound cis- 3, 4-cis-4, 5-cis-2, 5-bis-(4-hydroxyphenyl)-3, 4- healing. Since the role of free radicals in the physiology dimethyltetrahydrofuran lignan [25], and a known lignan, of wounds is clearly defined and the plants reported to (-)- secoisolaricircsinol [26] were identified from this contain anthocyanidins and tannoid principles have been plant both of which do not possess HIV–I reverse studied for potential antioxidant activity (Govindarajan transcriptase inhibitory activity (Rimando et al., 1994b). et al., 2005). Anolignan A [23], B [24] and C [25] isolated from A. acuminata were tested on cancer cell lines. Anolignan Activity-guided fractionation of butanolic fractions C [25] is the first example of all cis-isomer of lignans in of Anogeissus leiocarpus revealed hydrolysable tannins this group, other isolated compounds of such structure with a range of activity (MIC, 7.5–27.5 µg/ml or 14– from plants are, namely, (2α, 3β, 4β, 5α)-2, 5-bis- (4- 91 µM) (Shuaibu et al., 2008). Effect of the compounds hydroxyphenyl)-3, 4-dimethyltetrahydrofuran, 2, 3-trans- on fibroblasts did not reveal serious toxicity at moderate 2, 4-cis-2, 5-bis-(4-hydroxyphenyl) - 3, 4- concentration but is concentration dependent (Shuaibu dimethyltetrahydrofuran and its enantiomer, and 2,3- et al., 2008). trans-4, 5-trans-2, 5-bis-(4-hydroxyphenyl)- 3, 4- dimethyltetrahydrofuran. 2, 3-Diaryl-butadiene was Lin et al. (1991) extracted the bark of Anogeissus isolated from the stem of A. acuminata and the acuminata in aqueous acetone and by repeated column compound showed cytotoxicity for various cancer cell
Medicinal Plants, 1(2) July, 2009 Chemistry of secondary metabolites and antimicrobial activity in the drug development process 15
Table 4 : Distribution of miscellaneous compounds in Anogeissus species
Plant and Chemical compounds Category Plant Reference part
Anogeissus acuminata (DC.) Guill. & Perr.
2-(2',4'-Dihydroxybenzyl)-3-(3',4'-methylenedioxy-benzyl)- Lignan Bark Rimando et al., 1994a 1,3-butadiene (Anolignan A, [23])
2,3-bis-(4-Hydroxybenzyl)butadiene (Anolignan B, [24]) Lignan Bark Rimando et al., 1994a
2,3-cis-3,4-cis-4,5-cis-2,5-bis-(4-Hydroxyphenyl)-3,4- Lignan Bark Rimando et al., 1994a dimethyltetra hydrofuran lignan (Anolignan C, [25])
Medicinal Plants, 1(2) July, 2009 16 Mann et al.
Table 4 : Continued ......
Plant and Chemical compounds Category Plant Reference part
(-)-Secoisolariciresinol [26] Lignan Bark Rimando et al., 1994a
Leiocarpan A [27] Polysaccharide Bark Aspinall and Chaudhari, 1975
Pterostilbene [28] Stilbene Bark Rimando et al., 1994b
Medicinal Plants, 1(2) July, 2009 Chemistry of secondary metabolites and antimicrobial activity in the drug development process 17 lines and some of them also showed inhibitory activity containing glucose and mannose residues in alternating against HIV-1 reverse transcriptase in vitro (Rimando et sequences and 6-O-β-D-galactopyranosyl-D-galactose al., 1993). Anolignans from Anogeissus acuminata (VIII). It is concluded that the interior chains of showed synergistic inhibition of RTase of wild and drug- leiocarpan A contain alternate 4-O-substituted β-D- resistant HIV-1 strains. glucuronic acid and 2-O-substituted α-D-mannopyranose residues (Aspinall and McNab, 1969). The Stem exudates of Anogeissus species have been used trisaccharides, β-D-galactopyranosyl-(1,6)-β-D- as gums and attention has been given to the analyses galactopyranosyl-(1,3)-L- arabinose and β-D- of some of the constituents of these gums. For example, galactopyranosyl-(1,6)-β-D-galactopyranosyl-(1,6)-D- the commonest aldobiouronic acid present in gum, galactose were isolated from ‘marke’ gum from A. β acaciabiuronic acid (6-O- -D glucopyranosyl-D- schimperii (syn. A. leiocarpus). The disaccharide, 6-O- galactose), was isolated from the gum exudates of the β-D-xylopyranosyl-D-mannose was identified from A. plant, A. latifolia by partial hydrolysis of the gum leiocarpus whose major polysaccharide component of β (Aspinall et al., 1955). Aldobiouronic acid, 2-O- -D- gum exudates, leocarpin A which was reduced, gluconosyl-D-mannose, was also isolated from the gum. methylated and sugar content analysed quantitatively α The arabinose containing disaccharides, 3-O- -L- (Aspinall and Chaudhari, 1975). Gum exudates of A. arabinofuranosyl-L-arabinose arabinopyranobiose (3-O- schimperii was analysed for its proteinous components β β -arabinopyranosyl-L-arabinose) and 3-O- - (Anderson et al., 1987). Myriad of opportunities are galactopyranosyl-L- arabinose were all identified as part abound in genus Anogeissus that can provide chemical of the constituents of gum exudates of A. schimperii substances with significant therapeutic potentials after partial acid hydrolysis (Aspinall and Christenen, (Adigun et al., 2001 ; Chaabi et al., 2006 ; Chaabi et al., 1961; Aspinall et al., 1968). Also, the disaccharide, 6- 2008 ; Mann et al., 2007c ; 2008a,b,c ; Rimando et al., β O- -D-galactopyranosyl-D-galactose was identified from 1993; 1994a,b; 2002; Shuaibu et al., 2008). Pterostilbene the gum. Fractionation of Anogeissus leiocarpus gum [28] is a naturally-occurring phytoalexin identified in affords two distinct polysaccharides, leiocarpan A [27] several plant species. It belongs to a group of phenolic and leiocarpan B. Partial hydrolysis of leiocarpan A [27] compounds known as stilbenes. Pterostilbene [28] was furnishes a complex mixture of neutral and acidic also isolated from A. acuminata. Recent studies show β oligosaccharides including 3-O- -L-arabinofuranosyl-L- that pterostilbene has extensive activities such as β arabinose (I), 3-O- -L-arabinopyranosyl-L-arabinose (II), antifungal (5-fold than that of resveratrol), cancer β β 3-O- -D-galactopyranosyl-D-galactose (III), 6-O- -D- chemopreventive (Rimando et al., 2002; Suh et al., 2007), β galactopyranosyl-D-galactose (IV), 3-O- -D- cancer cell cytotoxic (Rimando et al., 2002; Rimando et β galactopyranosyl-L-arabinose (V), O- -D- al., 1994), antioxidant, and the most important, β galactopyranosyl-(1-6)-O- -D-galactopyranosyl-(1-3)- cholesterol-lowering (better than ciprofibrate) (Rimando β L-arabinose (VI), 6-O-( -D-glucopyranosyluronic acid)- et al., 2005), anti-diabetic (comparable to metformin) β D-galactose (VII), O-( -D-glucopyranosyluronic acid)- (Pari and Satheesh, 2006) and anti-inflammatory (Hougee (1-6)-O-D-galactopyranosyl-(1-3)-L-arabinose (VIII), 2-O- et al., 2005) activities. (β-D-glucopyranosyluronic acid)-D-mannose (IX), and O-(D-glucopyranosyluronic acid)-(1-2)-O-D- CONCLUSION mannopyranosyl-(1-4)-O-(D-glucopyranosyluronic acid)- (1-2)-D-mannose (X). Re-examination of the partial hydrolysis products from gum ghatti (from Anogeissus The genus Anogeissus is an unique source of numerous latifolia) has shown that the acidic tetrasaccharide (X) types of compounds having diverse chemical structures. is also formed from this polysaccharide (Aspinall et al., Even though some work has been done on the biological 1969). Methylation of degraded leiocarpan A followed activity of the isolated compounds of this genus, a lot by reduction and hydrolysis furnishes 2, 3, 4-tri-O- of them are yet to be investigated for therapeutic activity. methyl-D-xylose, 3, 4, 6-tri-, and 3, 4-di-O-methyl-D- Plausible medicinal applications of these compounds mannose, and 2, 3-di-O-methyl-D-glucose as the major and hence extensive investigation are needed to exploit products. Acetolysis of carboxy-reduced leiocarpan A their pharmaceutical utility to combat with diseases. A [27], followed by deacetylation, affords a mixture of drug-development programme should be undertaken to oligosaccharides including 2-O-β-D-glucopyranosyl-D- develop modern drugs with the compounds isolated mannose (I), 4-O-α-D-mannopyranosyl-D-glucose (II), from this genus. Although crude extracts from various and a series of higher oligosaccharides (III)–(VII) parts of plants of this genus have medicinal applications modern drugs can be developed after extensive
Medicinal Plants, 1(2) July, 2009 18 Mann et al. investigation of its bioactivity, mechanism of action, Phytochem. Oxford : Pergamon Press. 26(3) : 837-839. pharmacotherapeutics, and toxicity after proper Apparanantham T and Chelladurai V (1986). Glimpses on standardization and clinical trials. As the global scenario folk medicines of Dharmapuri forest division, Tamilnadu, is now changing towards the use of natural products Anc. Sci. Life, 5 : 182-185. Aruoma OI, Murcia A, Butler J and Halliwell B (1993). having medicinal use, development of modern drugs Evaluation of the antioxidant and pro-oxidant actions of from this genus should be emphasized for the control gallic acid and its derivatives. J. Agric. Food Chem., 41 of the world’s major diseases. Such diseases include : 1880-1885. cancer, HIV/AIDS, malaria, sickle cell anaemia, diabetes, Aspinall GO et al. (1968). 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Preliminary phytochemical and antimicrobial characterized by pterostilbene, and its activity in healthy screening of 50 medicinal plants from Nigeria. African human volunteers. Planta Med., 71 : 387-392. J. Biotechnol., 6(15) : 1690-1696. Ibrahim AM (1992). Anthelminitic activity of some Sudanese Kudi AC, Umoh JU, Eduvie LO and Gefu J (1999). Screening Medicinal plants, Phytother. Res., 6 : 155-157. of some Nigerian medicinal plants for antibacterial Ibrahim K, Nwamba CO, Mann A and Inyang US (2005). A activity. J. Ethnopharmacol., 67(2) : 225-228. preliminary Investigation into the antibacterial properties Latté KP and Kolodziej H (2000). Antifungal effects of of Anogeissus leiocarpus and Piper guineense seeds on hydrolysable tannins and related compounds on Staphylococcus aureus and Pseudomonas aeruginosa. dermatophyte, mould fungi and yeasts. Z. Naturforsch., Nig. J. App. Arts & Sci (NIJAAS), Maiden Edition: 21- 55c : 467-472. 24. 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Antibacterial Economic Plants of Nupeland. 1st Ed. Jube-Evans Books effect of the extracts of leaf, stem and root bark of and Publications, Bida, Niger State Nigeria, pp 276. Anogeissus leiocarpus on S. aureus NCTC 6571, S. Mann A (2007). Survey of Ethnomedicine for the treatment pyogenes NCTC, 8198, E. coli NCTC 10418 and P. of Tuberculosis: Chemistry Perspective. Ayanwola vulgaris NCTC 4638. J. Pharm. Res. Dev., 2(1) : 20-26. Printing Works, Minna, pp 117. Iinuma M, Tsuchiya H, Sato M, Yokoyama J, Ohyama M, Mann A, Amupitan JO, Oyewale AO, Okogun JI and Ibrahim Ohkawa Y, Tanaka T, Fujiwara S and Fuji T (1994). K (2007a). An Ethnobotanical survey of indigenous flora Flavonones with potent antibacterial activity against for treating tuberculosis and other respiratory diseases methicillin-resistant Staphylococcus aureus. J. Pharm., in Niger State, Nigeria. J. Phytomed. and Therap., 12 : Pharmacol. 46: 892-895. http:// 1-12. www.ethnopharmacology.org/iseConst.html Mann A, Yahaya AY and Suleiman ID (2007b). Ingle TR, Kulkarni VR and Viadya SH (1985). Preparation of Physicochemical studies of some fruits of Nigerian L-arabinose from Gum Ghatti (Anogeissus latifolia). medicinal plants used for treatment of respiratory Research and Industry, 30 : 369-373. diseases. Chem. Class Journal, 4 : 91-94. Izhaki I (2002). Emodin- a secondary metabolite with multiple Mann A, Amupitan JO, Oyewale AO, Okogun JI and Ibrahim ecological functions in higher plants. New Phytologist, K (2007c). Antimicrobial potentials of Anogeissus 155 : 205-217. leiocarpus and Terminalia avicennioides in treating Jain SK (1991). Dictionary of Indian folk Medicine and infectious diseases prevalent in Hospital Environments Ethnobotany. Deep Publications, New Delhi, India. in Nigeria. WITED Journal, Accepted in Press.
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Mann A, Banso A and Clifford LC (2008a). Antifungal plank-built catamarans. properties of Anogeissus leiocarpus and Terminalia Reddy KK, Rajadurai S and Nayudamma Y (1965). Studies avicennioides. Tanzania J. Health Res., 10 : 34-38. on Dhava (Anogeissus latifolia) tannins: Part III – Mann A, Yahaya AY, Banso A and Ajayi GO (2008b). Polyphenols of bark, sapwood and heartwood of Dhava. Phytochemical and antibacterial screening of Anogeissus Indian J. Chem., 3 : 308-310. leiocarpus against some microorganisms associated with Reddy KRS, Srimannarayana G and Subba NVR (1974). Curr. infectious wounds. Afr. J. Microb. Res., 2 : 60-62. Sci., 43 : 544. Mann A, Amupitan JO, Oyewale AO, Okogun JI, Ibrahim K, Rimando M, Pezzuto, JM, Farnsworth NR et al. (1993). Oladosu P, Lawson L, Olajide I and Nnamdi A (2008c). 206th ACS National Meeting, Division of Medicinal Evaluation of in vitro antimycobacterial activity of Chemistry, Chicago, IL, August 22-27, 1993, MEDI. 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Abdullahi Mann, Nigerian graduated with B.Sc (Hons) Degree in Chemistry and M.Sc Degree in Organic Chemistry, both from Bayero University, Kano, Nigeria and Ph.D (in view) in chemistry (Natural Product Chemistry) from Ahmadu Bello University, Zaria, Nigeria. He is a Chief Lecturer in the Department of Science Laboratory Technology, Federal Polytechnic, Bida, Nigeria. His research interests focus on natural product chemistry especially the screening of the extracts for activity against human and animal protozoans (Trypanosoma, malaria parasites), pathogenic bacteria (tuberculosis) and fungi; detection, isolation, and identification of biologically active secondary metabolites produced by higher plants. He has authored more than 50 scientific publications.
Dr Kolo Ibrahim graduated with B Sc [Medical Microbiology] in 1977, M Sc [Medical Microbiology] in 1982, and Ph D [Medical Microbiology] in 1991, all from Ahmadu Bello University Zaria, Nigeria. He took up appointment as a pupil Microbiologist with Niger State Government in 1998. He joined the services of National Institute for Pharmaceutical Research and Development, Abuja (NIPRD-Abuja) in 1992 as a Research Fellow, where he established the Department of Pharmaceutical Microbiology and Biotechnology and became its pioneer Head of Department. In 2002, he went on sabbatical leave in Federal University of Technology, Minna, Nigeria. He is currently the Director and Head of Department of Microbiology, Human Virology and Biotechnology of the institute. His research interests cover mycobacteriology, sourcing anti-Tuberculosis drugs from medicinal plants, and Antimicrobial drug screening and resistance. He is an active member of the NIPRD-NIH Tuberculosis collaborative team. He has authored over 38 scientific publications in various local and international journals and has a drug patented in US with patient number: NO. 5840 on the Antifungal product used for the treatment of skin fungal diseases.
Medicinal Plants, 1(2) July, 2009 Chemistry of secondary metabolites and antimicrobial activity in the drug development process 23
Professor Adebayo Ojo Oyewale graduated in Chemistry from Ahmadu Bello University, Zaria, Nigeria in 1985. In 1991 he received a Ph D in Organic Chemistry from University of St. Andrews, Scotland, UK on a British Petroleum Sponsorship. He holds a lectureship position since 1986 at Chemistry Department, Ahmadu Bello University, Zaria, Nigeria and is currently a Professor. His research fields are: synthetic organic chemistry, medicinal plant chemistry and analysis of organics in the environment.
Professor Joseph Olorunju Amupitan, Nigerian graduated from Ahmadu Bello University, Zaria, Nigeria with B Sc [Hons] Chemistry in 1973, and M Sc [Chemistry] in 1976. He proceeded to The Victoria University of Manchester UK where he obtained his PhD [Chemistry] degree in 1979. He obtained a SERC [UK] grant in the same University after which he returned to resume a lectureship position in Ahmadu Bello University rising to the rank of Professor in 1995. His areas of research interest are Organic Synthetic Methods and Medicinal Plant Chemistry.
Professor Joseph Ibomein Okogun graduated with B.Sc (London), PhD (Ibadan), DIC (London), C. Chem., FRSC, FCSN, FNSP, FAAS, FAS. Born in 1939 at Agbor, Delta State hails from Ewohimi in Edo State in Nigeria. He had his Postdoctoral Fellow as well as visiting Professor at Imperial College London with late Nobel Laureate Sir Derek H. R. Barton, Darmstadt Technische Hochschule Germany, and Hannover. Tierarzliche Hochschule, Germany with Gerhard Habermehl, H. Duddeck , H. Krebs and University of Hohenheim, Germany with W. Kraus. He was a Professor of Chemistry in University of Ibadan from 1977 to 1995. He is currently a Special Consultant Professor of Phytochemsitry at the National Institute for Pharmaceutical Research and Development, Abuja and an Adjunct Professor of Chemistry at the University of Ibadan, Ibadan. Research interests in natural products organic chemistry and ethnobotany.
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