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Introduction INTRODUCTION Section I: Bioactive Molecules from Mimusops elengi & Artemisia pallens Section II: Characterization of Molecules by Single Crystal X- Ray Diffraction Section I Bioactive Molecules from Mimusops elengi & Artemisia pailens 1.1 Ayurveda - The Art of Life Man has sought out plants with medicinal properties since ancient times. Evidence of this is the thousand years old traditions and records of proper healing. Traditional medicine (also known as indigenous or folk medicine) comprises medical knowledge systems that developed over centuries within various societies before the era of modern medicine. Traditional medicines include Unani system in Greece, Ayurvedic system in India, Amachi in Tibet, traditional Chinese medicine in China, Siddha or more recently Homoeopathy in Germany. Researchers are investigating not only the classical plants but also the related species that may contain similar active constituents as well as hitherto unknown plants which have no previous history of medicinal use\ Ayurveda is a holistic system of medicine from India that uses a constitutional model. Its aim is to provide guidance regarding food and lifestyle so that healthy people can stay healthy and folks with health challenges can improve their health. Ayurveda is an intricate system of healing that originated in India thousands of years ago. Vast ethno botanical knowledge exists in India from ancient time. Written records of the use of plants for curing human or animal diseases in India can be traced back to the earliest (4500-1600 BC) scripture of the Hindus, the Rigveda. Ayurveda, the Indian indigenous system of medicine dating back to Vedic ages (1500-800 BC), has been the integral part of Indian culture. Several plants were described in Atharvaveda. This was followed by monumental ancient treatise on the subject like Charak Samhita (1000-800 BC), Sushrut Samhita (800-700 BC) and Vagbhata's Ashtang Hridaya ^. As a science of life, Ayurveda is applicable to every living thing. The knowledge of Ayurveda is an integral part of the universal reality and manifests with each manifestation of the universe. In Ayurveda a person is viewed as a unique individual made up of five primary elements. The elements are ether (space), air, fire, water and earth. Just as in nature, we too have these five elements in us. Ether and air combine to form what is known in Ayurveda as the Vata dosha. Vata governs the principle of movement and therefore can be seen as the force which directs nerve impulses, circulation, respiration and elimination. Fire and water are the elements that combine to form the Pitta dosha. The Pitta dosha is the process of transformation or metabolism. The transformation of foods into nutrients that our bodies can assimilate is an example of a pitta function. Pitta is also responsible for metabolism in the organ and tissue systems as well as cellular metabolism. Finally, it is predominantly the water and earth elements which combine to form the Kapha dosha. Kapha is what is responsible for growth, adding structure unit by unit. Another function of the Kapha dosha is to offer protection. Cerebral- spinal fluid protects the brain with spinal column and is a type of Kapha found in the body. Also, the mucosal lining of the stomach is another example of the Kapha dosha protecting the tissues. We are all made up of unique proportions of Vata, Pitta and Kapha. These ratios of the doshas vary in each individual; and because of this, Ayurveda obsen/es each person as a special mixture that accounts for our diversity ^. The use of drugs and dietary supplements, derived from plants, has accelerated in recent years. Advances in science, notably during the last two centuries, better understanding of human body, and its physiology led to the isolation of many of the active ingredients of these herbs and plants in pure form and formulated synthetic compounds with or without herbal extracts, obtaining the drugs mostly used in the control of disease. The medicinal plants continue to receive attention of scientists from chemical, pharmacological and clinical angles in India and abroad. The studies on folk medicines through ethno botanical surveys are gaining importance'*. 1.2 Active Ingredients of Plants used as Drugs All plants produce chemical compounds as part of their normal metabolic activities. These include primary metabolites, such as sugars and fats, found in all plants, and secondary metabolites acquire in vahous proportions of active ingredients and only in a particular genus or species. The functions of secondary metabolites are varied, for example, some secondary metabolites are toxins used to deter predation, and others are pheromones used to attract insects for pollination. Phytoalexins protect against bacterial and fungal attacks. Allelochemicals inhibit rival plants that compete for soil and light. Organic chemicals from crude drugs provide a model which can be copied or modified by the organic chemist to produce a more potent drug or a better drug with fewer side effects. Many active principles have been isolated from plant sources such as digoxin (i) and acetyl digoxin (ii) from the Digitalis lanata leaf ^'®. Acetyl digoxin possesses cardio tonic and cardio toxic properties^. Plant-derived alkaloids have traditionally been of interest due to their pronounced physiological activities. Lopes F.C. et al isolated guanidine alkaloid pterogynidine (iii) from the Brazilian plant Alchornea glandulosa. It can be used potentially against pathological situations where angiogenesis is stimulated as tumor development^. Mentha longifolia L. (Lamiaceae) leaves have been traditionally implemented in the treatment of minor sore throat and minor mouth or throat irritation by the indigenous people of Iraq. Al-Bavati FA. reported antimicrobial activity of menthol (iv) and other isolates which validates the use of this plant in the treatment of minor sore throat and minor mouth or throat irritation^. The fruits and seeds of Semecarpus anacardium are used widely for the treatment of human cancers and other diseases in the Ayurvedic and Sidda systems of medicine in India. 3-(8'(Z),11'(Z)-pentadecadienyl) catechol (v) isolated from this plant is cytotoxic to tumor cell lines with IC(50) values lower than doxorubicin (vi) ^°, Gaultheria yunnanensis possesses analgesic and anti-inflammatory activities. The active principle of this is found to be gaultherin''^ (vii). Flavonoids, quercetin (viii) and kaempferol (ix) isolated from Danae racemosa are the active principles responsible for the antinociceptive action against several pain models^^, Scaphyglottis livida and Maxillaria densa are used in folk medicine for treatment of painful complaints. Activity of the isolated compounds in mice and rats support the popular use of this species ^^. Papaver somniferum, yields a sap of narcotic opium, from which the potent pain killer morphine (x) is made. Activator protein 1 is a transcription factor involved in the regulation of proinflammatory mediators'"*. For centuries, malaria was treated with the bark of Cinchona calisaya and Cinchona succirubra plants named "quinas" in Brazil. Quinine (xi) is the active principle isolated from chinchona plants. Other plant species like Deianira erubescens (roots and leaves), Strychnos pseudoquina (bark) and Remijia ferruginea (bark) are also used to treat fever and malana ^^. The history of aspihn (xii) can be traced back to ancient Egypt where extract of willow bark was used to treat inflammation. The active component of the extract was identified as the glucoside of salicylic alcohol. The severe gastric side effects associated with the use of sodium salicylate prompted the synthesis of the o-acetyl-derivative as a possible pro-drug. Acetylsalicylic acid was synthesized one hundred years ago and was mass-produced under the commercial name of 'Aspirin' ^^. The Madagascar periwinkle [Catharanthus roseus (L.) G. Don] is a plant species known for its production of terpenoid indole alkaloids (TIAs), many of which are pharmaceutically important. Ajmalicine (xiii) and serpentine (ivx) are preschbed for the treatment of hypertension, whereas the bisindoles vinblastine (xv), vincristine (xvi) and 3',4'-anhydrovinblastine (xvii) are used for their antineoplastic activity in the treatment of many cancers". Rauwolfia serpentine is reported to be the first herbal antipsychotic plant^^. It is used extensively in India for sleeplessness, anxiety and high blood pressure^^. Reserpine (xviii) and deserpidine (xix) alkaloids are the active principals from Rauwolfia species which are responsible for their antihypertensive action^°. A plant flavonide quercetin -3-0-glucoside (Q3G) isolated by preparative HPLC from aerial parts of Prangos ferulaceae is cytotoxic, phytotoxic, antimicrobial and antioxidant ^^ Medicinal plants are also reported to be useful for the treatment of diseases like eye infections. IHippobromus pauciflorus was the most commonly used plant species ^^. Seeds of Murraya l<oenigii Spreng (Rutaceae) resulted in the isolation of three bioactive carbazole alkaloids, kurryam (xx), koenimbine (xxi) and koenine (xxii). The compounds produced a significant reduction in gastrointestinal motility in the charcoal meal test in Wister rats ^^. Vasicine (xxiii) is a pyrrolazoquinazoline alkaloid obtained from the leaves of Adhatoda vasica which is a highly reputed ayurvedic medicinal plant used for the treatment of respiratory ailments, particularly for the treatment of cough, bronchitis, asthma and tuberculosis^'*. Piperine (xxiv) is
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