DOCSLIB.ORG

Role of Indole Scaffolds As Pharmacophores in The

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Role of Indole Scaffolds As Pharmacophores in The molecules Review Role of Indole Scaffolds as Pharmacophores in the Development of Anti-Lung Cancer Agents Jyothi Dhuguru and Rachid Skouta * Department of Biology, University of Massachusetts, Amherst, MA 01003, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-413-577-4167 Received: 13 February 2020; Accepted: 30 March 2020; Published: 1 April 2020 Abstract: Lung cancer is the leading cause of death in men and women worldwide, affecting millions of people. Between the two types of lung cancers, non-small cell lung cancer (NSCLC) is more common than small cell lung cancer (SCLC). Besides surgery and radiotherapy, chemotherapy is the most important method of treatment for lung cancer. Indole scaffold is considered one of the most privileged scaffolds in heterocyclic chemistry. Indole may serve as an effective probe for the development of new drug candidates against challenging diseases, including lung cancer. In this review, we will focus on discussing the existing indole based pharmacophores in the clinical and pre-clinical stages of development against lung cancer, along with the synthesis of some of the selected anti-lung cancer drugs. Moreover, the basic mechanism of action underlying indole based anti-lung cancer treatment, such as protein kinase inhibition, histone deacetylase inhibition, DNA topoisomerase inhibition, and tubulin inhibition will also be discussed. Keywords: lung cancer; indole; non-small cell lung cancer; kinase inhibition; apoptosis; DNA topoisomerase, histone deacetylase inhibition 1. Introduction Lung cancer remains the deadliest disease on record, with approximately 2.09 million new cases reported each year. According to the World Health Organization, it is responsible for 1.7 million cancer deaths worldwide per year [1]. There are two major types of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Among these two types of lung cancers, NSCLC is responsible for approximately 80%–90% of cancerous tumors [2,3]. NSCLC is further divided into three major histological subtypes: squamous-cell carcinoma, adenocarcinoma, and large-cell carcinoma. SCLC and squamous-cell carcinoma are strongly linked to smoking, while adenocarcinoma is the most common type of lung cancer in patients who have never smoked [4]. Treatment of lung cancer is commonly addressed by surgical removal of the affected area and by chemotherapy, which applies a combination of one or more drugs in conjunction with radiation therapy. However, multidrug resistance and the severe side effects associated with chemotherapy persists as one of the major challenges in the treatment of lung cancer. 1.1. Indole and its Pharmacological Significance Indole is a pervasive and naturally occurring heterocyclic compound, the structure of which comprises of a six-membered benzene ring tethered to a five-membered pyrrole ring [5] (Figure1). With its 10 π-electrons, indole follows Huckel’s rule of aromaticity. It is more prone to electrophilic substitution reactions similar to the benzene ring. Molecular orbital studies showed that the 3-position of indole is more reactive towards the electrophilic substitution reactions. Indoles can undergo N-substitution reactions under basic conditions owing to the slightly acidic nature of the—NH bond in Molecules 2020, 25, 1615; doi:10.3390/molecules25071615 www.mdpi.com/journal/molecules Molecules 2019, 24, x FOR PEER REVIEW 2 of 26 [7]. Due to the diverse applications of the indole scaffold in both the biological and pharmacological fields, hundreds of synthetic schemes were published. The most prominent and widely used ones are Molecules 20202019,, 2524,, 1615x FOR PEER REVIEW 2 of 2526 those reported by Fisher [8], Bischler [9], Hemetsberger [10], Nenitzescu [11], Bartoli [12], and others [13,14]. [7]. Due to the diverse applications of the indole scaffold in both the biological and pharmacological indoleOwing [6]. The to firstits bioavailability synthesis of indole and waspharmacological accomplished applications, in 1866 by Adolf indole von is Baeyer considered [7]. Due the tomost the fields, hundreds of synthetic schemes were published. The most prominent and widely used ones are privileged scaffold in heterocyclic chemistry with such widespread applications as antiviral, diversethose reported applications by Fisher of the [8], indole Bischler scaff [9],old Hemetsberger in both the biological [10], Nenitzescu and pharmacological [11], Bartoli fields,[12], and hundreds others of[13,14].antimicrobial, synthetic schemes anti-inflammatory, were published. anti-cancer, The most prominentanti-hypertensive, and widely anti-diabetic, used ones and are those antioxidant reported [15– by Fisher17]. Owing [8], Bischler to its bioavailability [9], Hemetsberger and [ 10pharmacological], Nenitzescu [11 applications,], Bartoli [12 ],indole and others is considered [13,14]. the most privileged scaffold in heterocyclic chemistry with such widespread applications as antiviral, antimicrobial, anti-inflammatory, anti-cancer, anti-hypertensive, anti-diabetic, and antioxidant [15– 17]. FigureFigure 1.1. Structure of indole. Owing to its bioavailability and pharmacological applications, indole is considered the most 1.2. Natural Abundance of Indoles privileged scaffold in heterocyclic chemistry with such widespread applications as antiviral, antimicrobial,Naturally anti-inflammatory, occurring indole anti-cancer, derivatives,Figure 1. anti-hypertensive, Structure such as of indole.glucobrassicin anti-diabetic, and andindole-3-carbinol, antioxidant [15– 17are]. commonly found in cruciferous vegetables like cabbage, broccoli, and sprouts [18]. Indole-3-carbinol 1.2.and Natural its dimeric Abundance product of 3,3’-diindolylmethaneIndoles have been found to induce apoptosis in cancer cells [18]. This is a property that has increasingly commanded the attention of researchers from around Naturally occurringoccurring indole indole derivatives, derivatives, such such as glucobrassicin as glucobrassicin and indole-3-carbinol, and indole-3-carbinol, are commonly are the world. To get the greatest benefits, indole rich sources belonging to the Brassica family are foundcommonly in cruciferous found in cruciferous vegetables vegetables like cabbage, like broccoli,cabbage, andbroccoli, sprouts and [sprouts18]. Indole-3-carbinol [18]. Indole-3-carbinol and its particularly recommended by the National Cancer Institute to reduce the risk of cancer [18]. dimericand its dimeric product product 3,30-diindolylmethane 3,3’-diindolylmethane have been have found been to inducefound apoptosisto induce inapoptosis cancer cells in cancer [18]. This cells is a[18]. property TryptophanThis is that a property has containing increasingly that hasindole commanded increasingly is an essential the commanded attention amino ofacid the researchers foundattention in from many of researchers around natural the resources. world.from around To It get is thealso greatestworld. a biosynthetic benefits,To get theprecursor indole greatest rich for sourcesbenefits, the tryptamine, belonging indole rich to5-hydroxy-tryptophan, the sources Brassica belonging family are toan particularly theimmediate Brassica recommended precursor family are of byparticularlyserotonin the National (Figure recommended Cancer 2). Institute by the to National reduce the Cancer risk of Institute cancer [to18 reduce]. the risk of cancer [18]. Tryptophan containingcontaining indole is an essentialessential amino acid found in manymany naturalnatural resources.resources. It is also a biosynthetic precursor for thethe tryptamine,tryptamine, 5-hydroxy-tryptophan,5-hydroxy-tryptophan, an immediate precursor of serotonin (Figure2 2).). Figure 2. Indole scaffold in biologically important compounds. Serotonin (5-hydroxytryptamine) is an important neurotransmitter associated with the transmission of nerve impulses. It further serves as a precursor to melatonin, a neuro-hormone Figure 2. IndoleIndole scaffold scaffold in biologically important compounds. secreted by the pineal gland. Besides, melatonin is involved in several physiological processes beyond the circadian rhythm [19,20]. Indole-3-acetic acid is the most common and widely studied Serotonin (5-hydroxytryptamine) is an importantimportant neurotransmitter associated with the transmissionplant hormones of of nervenerve the auxin impulses.impulses. class It(Figure It further further 2) [21].serves serves It isas as also a precursorprecurso the normalr to urinary melatonin,melatonin, tryptophan a neuro-hormoneneuro-hormone metabolite secretedobserved byby to the bethe pinealelevated pineal gland. ingland. patients Besides, Besides, wi melatoninth variousmelatonin is forms involved is involvedof liver in several disease in several physiological [22]. physiological processes processes beyond thebeyond circadian the circadian rhythm rhythm [19,20]. [19,20]. Indole-3-acetic Indole-3-acetic acid is acid the mostis the common most common and widely and widely studied studied plant 1.3. Significance of Indole Based Drugs hormonesplant hormones of the of auxin the auxin class class (Figure (Figure2)[ 212)]. [21]. It isIt is also also the the normal normal urinary urinary tryptophantryptophan metabolitemetabolite observedDelavirdine to be elevated is an inindole patients based withwith variousvariousanti-retroviral formsforms ofofdrug liverliver diseasediseaseapproved [[22].22 ].by the Food and Drug Administration (FDA) in 1997 for the treatment of HIV patients (Figure 3). The drug acts as a non- 1.3. Significance
Load more

Recommended publications
  • The Catechol-O-Methyltransferase Inhibitory Potential of Z
    Revista Brasileira de Farmacognosia 25 (2015) 382–386 www .sbfgnosia.org.br/revista Original Article The catechol-O-methyltransferase inhibitory potential of Z-vallesiachotamine by in silico and in vitro approaches a,b,1 a,1 a Carolina dos Santos Passos , Luiz Carlos Klein-Júnior , Juliana Maria de Mello Andrade , c a,∗ Cristiane Matté , Amélia Teresinha Henriques a Laboratório de Farmacognosia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil b Department of Pharmacochemistry, School of Pharmaceutical Sciences, Université de Genève, Genève, Switzerland c Programa de Pós-graduac¸ ão em Ciências Biológicas: Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil a b s t r a c t a r t i c l e i n f o Article history: Z-Vallesiachotamine is a monoterpene indole alkaloid that has a ␤-N-acrylate group in its structure. Received 29 May 2015 This class of compounds has already been described in different Psychotria species. Our research group Accepted 3 July 2015 observed that E/Z-vallesiachotamine exhibits a multifunctional feature, being able to inhibit targets Available online 26 July 2015 related to neurodegeneration, such as monoamine oxidase A, sirtuins 1 and 2, and butyrylcholinesterase enzymes. Aiming at better characterizing the multifunctional profile of this compound, its effect on Keywords: cathecol-O-methyltransferase activity was investigated. The cathecol-O-methyltransferase activity was Monoterpene indole alkaloids evaluated in vitro by a fluorescence-based method, using S-(5 -adenosyl)-l-methionine as methyl donor Vallesiachotamine and aesculetin as substrate. The assay optimization was performed varying the concentrations of methyl Catechol-O-methyltransferase l Docking donor (S-(5 -adenosyl)- -methionine) and enzyme.
    [Show full text]
  • Electrooxidation Enables Highly Regioselective Dearomative Annulation of Indole and Benzofuran Derivatives
    ARTICLE https://doi.org/10.1038/s41467-019-13829-4 OPEN Electrooxidation enables highly regioselective dearomative annulation of indole and benzofuran derivatives Kun Liu1, Wenxu Song1, Yuqi Deng1, Huiyue Yang1, Chunlan Song1, Takfaoui Abdelilah1, Shengchun Wang 1, Hengjiang Cong 1, Shan Tang1 & Aiwen Lei1* 1234567890():,; The dearomatization of arenes represents a powerful synthetic methodology to provide three-dimensional chemicals of high added value. Here we report a general and practical protocol for regioselective dearomative annulation of indole and benzofuran derivatives in an electrochemical way. Under undivided electrolytic conditions, a series of highly functio- nalized five to eight-membered heterocycle-2,3-fused indolines and dihydrobenzofurans, which are typically unattainable under thermal conditions, can be successfully accessed in high yield with excellent regio- and stereo-selectivity. This transformation can also tolerate a wide range of functional groups and achieve good efficiency in large-scale synthesis under oxidant-free conditions. In addition, cyclic voltammetry, electron paramagnetic resonance (EPR) and kinetic studies indicate that the dehydrogenative dearomatization annulations arise from the anodic oxidation of indole into indole radical cation, and this process is the rate- determining step. 1 College of Chemistry and Molecular Sciences, Institute for Advanced Studies (IAS), Wuhan University, Wuhan 430072, P. R. China. *email: aiwenlei@whu. edu.cn NATURE COMMUNICATIONS | (2020) 11:3 | https://doi.org/10.1038/s41467-019-13829-4 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-13829-4 reaking the aromatic systems of electron-rich arenes or fused indolines (Fig. 1a)39–44. Therefore, it is highly appealing to heteroarenes provides three-dimensional chemicals of high develop efficient approaches to allow for their preparation.
    [Show full text]
  • Links Between Genetic Groups, Indole Alkaloid Profiles and Ecology Within the Grass-Parasitic Claviceps Purpurea Species Complex
    Toxins 2015, 7, 1431-1456; doi:10.3390/toxins7051431 OPEN ACCESS toxins ISSN 2072-6651 www.mdpi.com/journal/toxins Article Links between Genetic Groups, Indole Alkaloid Profiles and Ecology within the Grass-Parasitic Claviceps purpurea Species Complex Mariell Negård 1,2, Silvio Uhlig 1,3, Håvard Kauserud 2, Tom Andersen 2, Klaus Høiland 2 and Trude Vrålstad 1,2,* 1 Norwegian Veterinary Institute, P.O. Box 750 Sentrum, 0106 Oslo, Norway; E-Mails: [email protected] (M.N.); [email protected] (S.U.) 2 Department of Biosciences, University of Oslo, P.O. Box 1066 Blindern, 0316 Oslo, Norway; E-Mails: [email protected] (H.K.); [email protected] (T.A.); [email protected] (K.H.) 3 Department of the Chemical and Biological Working Environment, National Institute of Occupational Health, P.O. Box 8149 Dep, 0033 Oslo, Norway * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +47-2321-6247. Academic Editor: Christopher L. Schardl Received: 3 January 2015 / Accepted: 22 April 2015 / Published: 28 April 2015 Abstract: The grass parasitic fungus Claviceps purpurea sensu lato produces sclerotia with toxic indole alkaloids. It constitutes several genetic groups with divergent habitat preferences that recently were delimited into separate proposed species. We aimed to 1) analyze genetic variation of C. purpurea sensu lato in Norway, 2) characterize the associated indole alkaloid profiles, and 3) explore relationships between genetics, alkaloid chemistry and ecology. Approximately 600 sclerotia from 14 different grass species were subjected to various analyses including DNA sequencing and HPLC-MS.
    [Show full text]
  • Heterocycles 2 Daniel Palleros
    Heterocycles 2 Daniel Palleros Heterocycles 1. Structures 2. Aromaticity and Basicity 2.1 Pyrrole 2.2 Imidazole 2.3 Pyridine 2.4 Pyrimidine 2.5 Purine 3. Π-excessive and Π-deficient Heterocycles 4. Electrophilic Aromatic Substitution 5. Oxidation-Reduction 6. DNA and RNA Bases 7. Tautomers 8. H-bond Formation 9. Absorption of UV Radiation 10. Reactions and Mutations Heterocycles 3 Daniel Palleros Heterocycles Heterocycles are cyclic compounds in which one or more atoms of the ring are heteroatoms: O, N, S, P, etc. They are present in many biologically important molecules such as amino acids, nucleic acids and hormones. They are also indispensable components of pharmaceuticals and therapeutic drugs. Caffeine, sildenafil (the active ingredient in Viagra), acyclovir (an antiviral agent), clopidogrel (an antiplatelet agent) and nicotine, they all have heterocyclic systems. O CH3 N HN O O N O CH 3 N H3C N N HN N OH O S O H N N N 2 N O N N O CH3 N CH3 caffeine sildenafil acyclovir Cl S N CH3 N N H COOCH3 nicotine (S)-clopidogrel Here we will discuss the chemistry of this important group of compounds beginning with the simplest rings and continuing to more complex systems such as those present in nucleic acids. Heterocycles 4 Daniel Palleros 1. Structures Some of the most important heterocycles are shown below. Note that they have five or six-membered rings such as pyrrole and pyridine or polycyclic ring systems such as quinoline and purine. Imidazole, pyrimidine and purine play a very important role in the chemistry of nucleic acids and are highlighted.
    [Show full text]
  • Synbiotics Alleviate the Gut Indole Load and Dysbiosis in Chronic Kidney Disease
    cells Article Synbiotics Alleviate the Gut Indole Load and Dysbiosis in Chronic Kidney Disease Chih-Yu Yang 1,2,3,4 , Ting-Wen Chen 5,6 , Wan-Lun Lu 5, Shih-Shin Liang 7,8 , Hsien-Da Huang 5,†, Ching-Ping Tseng 4,5,* and Der-Cherng Tarng 1,3,4,9,* 1 Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan; [email protected] 2 Stem Cell Research Center, National Yang-Ming University, Taipei 11221, Taiwan 3 Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan 4 Center for Intelligent Drug Systems and Smart Bio-Devices (IDS2B), Hsinchu 30010, Taiwan 5 Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan; [email protected] (T.-W.C.); [email protected] (W.-L.L.); [email protected] (H.-D.H.) 6 Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 30010, Taiwan 7 Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; [email protected] 8 Institute of Biomedical Science, College of Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan 9 Department and Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan * Correspondence: [email protected] (C.-P.T.); [email protected] (D.-C.T.) † Current affiliation: Warshel Institute for Computational Biology, School of Life and Health Sciences, The Chinese University of Hong Kong, Longgang District, Shenzhen 518172, China. Abstract: Chronic kidney disease (CKD) has long been known to cause significant digestive tract pathology.
    [Show full text]
  • Organophotocatalytic Dearomatization of Indoles, Pyrroles and Benzo(Thio)Furans Via a Giese-Type Transformation
    ARTICLE https://doi.org/10.1038/s42004-021-00460-y OPEN Organophotocatalytic dearomatization of indoles, pyrroles and benzo(thio)furans via a Giese-type transformation Yueteng Zhang1, Peng Ji1, Feng Gao1, Yue Dong1, He Huang2, Changqing Wang1, Ziyuan Zhou3 & ✉ Wei Wang 1 Accessing fascinating organic and biological significant indolines via dearomatization of indoles represents one of the most efficient approaches. However, it has been difficult for the dearomatization of the electron deficient indoles. Here we report the studies leading to 1234567890():,; developing a photoredox mediated Giese-type transformation strategy for the dear- omatization of the indoles. The reaction has been implemented for chemoselectively breaking indolyl C=C bonds embedded in the aromatic system. The synthetic power of this strategy has been demonstrated by using structurally diverse indoles bearing common electron- withdrawing groups including (thio)ester, amide, ketone, nitrile and even aromatics at either C2 or C3 positions and ubiquitous carboxylic acids as radical coupling partner with high trans- stereoselectivity (>20:1 dr). This manifold can also be applied to other aromatic heterocycles including pyrroles, benzofurans and benzothiophenes. Furthermore, enantioselective dear- omatization of indoles has been achieved by a chiral camphorsultam auxiliary with high diastereoselectivity. 1 Departments of Pharmacology and Toxicology and Chemistry and Biochemistry, and BIO5 Institute, University of Arizona, Tucson, AZ, USA. 2 Department of Chemistry and Chemical
    [Show full text]
  • Strictosidinic Acid, Isolated from Psychotria Myriantha Mull
    Fitoterapia 83 (2012) 1138–1143 Contents lists available at SciVerse ScienceDirect Fitoterapia journal homepage: www.elsevier.com/locate/fitote Strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae), decreases serotonin levels in rat hippocampus F.M. Farias a, C.S. Passos b, M.D. Arbo c, D.M. Barros d, C. Gottfried e, V.M. Steffen c, A.T. Henriques b,⁎ a Curso de Farmácia, Universidade Federal do Pampa, BR 472 km 592, CEP 97500‐970, Uruguaiana, RS, Brazil b Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, CEP 90610‐000, Porto Alegre, RS, Brazil c Laboratório de Toxicologia, Departamento de Análises, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, CEP 90610‐000, Porto Alegre, RS, Brazil d Programa de Pós-Graduação em Educação em Ciências, Química da Vida e Saúde, Universidade Federal de Rio Grande, Av. Itália, Km 8, CEP 96501‐900, Rio Grande, RS, Brazil e Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, CEP 90035‐003, Porto Alegre, RS, Brazil article info abstract Article history: Psychotria is a complex genus whose neotropical species are known by the presence of glucosidic Received 20 February 2012 monoterpene indole alkaloids. These compounds are able to display a large range of effects on the Accepted in revised form 11 April 2012 central nervous system, such as anxiolytic, antidepressant, analgesic, and impairment of learning Available online 21 April 2012 and memory acquisition. The aims of this study were to investigate the effects displayed by strictosidinic acid, isolated from Psychotria myriantha Mull.
    [Show full text]
  • The Relationship Between Growth and Indole-3-Acetic Acid Content of Roots of Pisum Sativum L
    The Relationship between Growth and Indole-3-Acetic Acid Content of Roots of Pisum sativum L. Author(s): William L. Pengelly and John G. Torrey Reviewed work(s): Source: Botanical Gazette, Vol. 143, No. 2 (Jun., 1982), pp. 195-200 Published by: The University of Chicago Press Stable URL: http://www.jstor.org/stable/2474706 . Accessed: 03/04/2012 15:52 Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at . http://www.jstor.org/page/info/about/policies/terms.jsp JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact [email protected]. The University of Chicago Press is collaborating with JSTOR to digitize, preserve and extend access to Botanical Gazette. http://www.jstor.org BOT. GAZ. 143(2):195-200. 1982. ? 1982 by The Universityof Chicago. All rightsreserved. 0006-8071/82/4302-0004$02.00 THE RELATIONSHIP BETWEEN GROWTH AND INDOLE-3-ACETIC ACID CONTENT OF ROOTS OF PISUM SATIVUM L. WILLIAM L. PENGELLY1 AND JOHN G. TORREY Cabot Foundation,Harvard University,Petersham, Massachusetts 01366 The indole-3-aceticacid (IAA) contentof roots and shoots of light-grownpea seedlings(Pisizmi sali,zim L. 'Little Marvel') growingat differentrates was studied by radioimmunoassayduring the firstweek of germination.Different growth rates were obtained by daily irrigationwith either deionized water or a dilute Hoagland's mineralnutrient solution.
    [Show full text]
  • One Hundred Years of Benzotropone Chemistry
    One hundred years of benzotropone chemistry Arif Dastan*1, Haydar Kilic2,3 and Nurullah Saracoglu*1 Review Open Access Address: Beilstein J. Org. Chem. 2018, 14, 1120–1180. 1Department of Chemistry, Science Faculty, Atatürk University, doi:10.3762/bjoc.14.98 25240, Erzurum, Turkey, 2Oltu Vocational Training School, Atatürk University, 25400, Erzurum, Turkey and 3East Anotolia High Received: 27 December 2017 Technology Application and Research Center, Atatürk University, Accepted: 20 April 2018 25240, Erzurum, Turkey Published: 23 May 2018 Email: Associate Editor: B. Stoltz Arif Dastan* - [email protected]; Nurullah Saracoglu* - [email protected] © 2018 Dastan et al.; licensee Beilstein-Institut. License and terms: see end of document. * Corresponding author Keywords: benzotropolone; benzotropone; dibenzotropone; halobenzotropolone; halobenzotropone; tribenzotropone; tropone Abstract This review focuses on the chemistry of benzo-annulated tropones and tropolones reported since the beginning of the 20th century, which are currently used as tools by the synthetic and biological communities. Review 1. Introduction Tropone (1) and tropolone (2) have fascinated organic chemists have been reported in the literature in a number of natural forms for well over one hundred years. The carbocycles 1 and 2 are a (Figure 1) [1-8]. These compounds have a structural class special variety of organic compounds and represent a nonben- spacing from the simple monocyclic tropones, such as the po- zenoid type of aromatic system (Scheme 1). Their dipolar reso- tent antifungal and antibiotic monoterpene β-thujaplicin (4) nance structures such as tropylium oxide form 1B and 2B have [17-23] (isolated from the heartwood and essential oils of trees been reported to provide a Hückel sextet of electrons that is of the family Cupressaceae), to complex macrocyclic ana- necessary for aromaticity (Scheme 1) [1-9].
    [Show full text]
  • Heterocyclic Chemistrychemistry
    HeterocyclicHeterocyclic ChemistryChemistry Professor J. Stephen Clark Room C4-04 Email: [email protected] 2011 –2012 1 http://www.chem.gla.ac.uk/staff/stephenc/UndergraduateTeaching.html Recommended Reading • Heterocyclic Chemistry – J. A. Joule, K. Mills and G. F. Smith • Heterocyclic Chemistry (Oxford Primer Series) – T. Gilchrist • Aromatic Heterocyclic Chemistry – D. T. Davies 2 Course Summary Introduction • Definition of terms and classification of heterocycles • Functional group chemistry: imines, enamines, acetals, enols, and sulfur-containing groups Intermediates used for the construction of aromatic heterocycles • Synthesis of aromatic heterocycles • Carbon–heteroatom bond formation and choice of oxidation state • Examples of commonly used strategies for heterocycle synthesis Pyridines • General properties, electronic structure • Synthesis of pyridines • Electrophilic substitution of pyridines • Nucleophilic substitution of pyridines • Metallation of pyridines Pyridine derivatives • Structure and reactivity of oxy-pyridines, alkyl pyridines, pyridinium salts, and pyridine N-oxides Quinolines and isoquinolines • General properties and reactivity compared to pyridine • Electrophilic and nucleophilic substitution quinolines and isoquinolines 3 • General methods used for the synthesis of quinolines and isoquinolines Course Summary (cont) Five-membered aromatic heterocycles • General properties, structure and reactivity of pyrroles, furans and thiophenes • Methods and strategies for the synthesis of five-membered heteroaromatics
    [Show full text]
  • 78719 Kovac's Reagent Strips (Indole Reagent Test Strips According to Kovac)
    78719 Kovac's Reagent Strips (Indole Reagent Test strips according to Kovac) For determination of the ability of microorganisms, primarily Enterobacteriaceae, to split indole from the tryptophan molecule by tryptophanases. Tryptophanase present in e.g. E. coli cleaves tryptophan to indole and pyruvic acid and ammonia. p-Aminobenzaldehyde present in the reagent builds with indole a pink complex. Composition: (1 package contains 25 strips) Sterile filter paper strips impregnated with Kovac`s Reagent Kovac`s reagent is prepared by dissolving 10 g of p-aminobenzaldehyde in 150 ml of isoamylalcohol and then slowly adding 50 ml of concentrated hydrochloric acid. Directions: Indole production by the organism is observed by inserting the Kovac's Reagent Strips between the plug and inner wall of the tube, above the inoculated Peptone Water (Cat. No. 70179) and incubated at 35°C for 18-24 hours. Quality control: Cultural response after 18-24 hours at 35°C in Peptone Water (Cat. No. 70179). Pink coloration of the lower part of the strip is a positive reaction and means microorganisms possess tryptophanase activity. A negative reaction shows no color change. Test Organisms (ATCC) Indole production Escherichia coli (25922) + Enterobacter aeogenes (13048) - 1. Control 2. Escherichia coli 3. Staphylococcus aureus Page 1 of 2 References: 1. J.F. MacFaddin, Biochemical Tests for Identification of Medical Bacteria, 2nd ed., Williams and Wilkins, Baltimore (1980) 2. A.E. Greenberg, R.R. Trussell, L.S. Clesceri (Eds.), Standard Methods for the Examination of Water and Wastewater, 16th ed., A.P.H.A, Washington, D.C. (1985) Precautions and Disclaimer This product is for R&D use only, not for drug, household, or other uses.
    [Show full text]
  • Tryptophan Catabolism by Lactobacillus Spp. : Biochemistry and Implications on Flavor Development in Reduced-Fat Cheddar Cheese
    Utah State University DigitalCommons@USU All Graduate Theses and Dissertations Graduate Studies 5-1998 Tryptophan Catabolism by Lactobacillus spp. : Biochemistry and Implications on Flavor Development in Reduced-Fat Cheddar Cheese Sanjay Gummalla Utah State University Follow this and additional works at: https://digitalcommons.usu.edu/etd Part of the Food Chemistry Commons, Food Microbiology Commons, and the Food Processing Commons Recommended Citation Gummalla, Sanjay, "Tryptophan Catabolism by Lactobacillus spp. : Biochemistry and Implications on Flavor Development in Reduced-Fat Cheddar Cheese" (1998). All Graduate Theses and Dissertations. 5454. https://digitalcommons.usu.edu/etd/5454 This Thesis is brought to you for free and open access by the Graduate Studies at DigitalCommons@USU. It has been accepted for inclusion in All Graduate Theses and Dissertations by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. TRYPTOPHAN CATABOLISM BY LACTOBACILLUS SPP.: BIOCHEMISTRY AND IMPLICATIONS ON FLAVOR DEVELOPMENT IN REDUCED-FAT CHEDDAR CHEESE by Sanjay Gummalla A thesis submitted in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE m Nutrition and Food Sciences Approved: UTAH STATE UNIVERSITY Logan, Utah 1998 11 Copyright © Sanjay Gummalla 1998 All Rights Reserved w ABSTRACT Tryptophan Catabolism by Lactobacillus spp. : Biochemistry and Implications on Flavor Development in Reduced-Fat Cheddar Cheese by Sanjay Gummalla, Master of Science Utah State University, 1998 Major Professor: Dr. Jeffery R. Broadbent Department: Nutrition and Food Sciences Amino acids derived from the degradation of casein in cheese serve as precursors for the generation of key flavor compounds. Microbial degradation of tryptophan (Trp) is thought to promote formation of aromatic compounds that impart putrid fecal or unclean flavors in cheese, but pathways for their production have not been established.
    [Show full text]