Chemical investigation of Indian medicinal plants in search of bioactive compounds

Abstract

Since ancient times man has relied on plants for food, shelter and healing agents. The earliest mention of the plants as drugs can be traced back to Rig Veda, which is considered to be the oldest repository of human knowledge. The WHO estimated that 80% of the world population still relies on herbs as its major source of medicinal products. Despite tremendous advances in modern medicine through chemotherapy, vaccines and diagnostics, even today indigenous drugs continue to be of interest not only to the scientists but to the health providers and layman alike because plant based drugs are not only effective but have better compatibility with human systems. Advancement in the organic chemistry since in the early part of the nineteenth century and refinement in the methods of purification, isolation and characterization of the active principles from the medicinal plants empowered the natural product chemistry. Presently nearly 25% of all the prescriptions of modern medicine contain one or the other drug of plant origin. Some of the important plant based drugs are artimisinine (antimalarial) from Artimisia anua, quinine as antimalarial and antipyretic from Cinchona lederiana, digoxin as cardiotonic from Digitalis purpurea, etoposide as antitumor agent from Podophyllum peltatum, morphine as analgesic from Papaver somminiferum, reserpine as antihypertensive from Rauwolfia serpentine, taxol as antitumor from Taxux brevifolia, vincristine and vinblastine as antitumor and antileukemic agent from Cantharanthus roseus, L-Dopa as anti-parkinsonism from Mucuna sp, silymarein as antihepatotoxic from Silybum marianum. The value of natural products can be assessed using three criteria: (1) the rate of introduction of new chemical entities of wide structural diversity, including serving as templates for semi-synthetic and total synthetic modification (2) the number of diseases treated or prevented by these substances and (3) their frequency of use in the treatment of disease. An analysis of the origin of the drugs developed between 1981 and 2002 showed that natural products or natural product derived drugs comprised 28% of all new chemical entities (NCEs) launched onto the market. In addition, 24% of these NCEs were synthetic or natural mimic compounds, based on the study of pharmacophore related to natural products. This combined percentage (52% of all NCEs) suggests that natural products are important sources for new drugs and are also good lead compounds suitable for further modification during drug development. Natural products have been the traditional pathfinder of compounds with an untold diversity of chemical structures unparalleled and unmatched even by the largest combinatorial libraries. There is a clarion calls for new antibiotics, chemotherapeutic agents and agrochemicals that are highly effective, cost-effective, possess low toxicity and have minimal side effects. The ingress to the human population of new disease causing agents such as HIV, Ebola and SARS and disorders like diabetes and dyslipidemia requires the discovery and development of new drugs to combat them. Not only do diseases like AIDS require drugs that target them specifically, but new therapies are needed for treating ancillary infections which are a consequence of a weakened immune system. In addition more drugs are needed to efficiently treat parasitic protozoan and nematodal infections such as malaria, leishmaniasis, trypanosomiasis and filariasis. Among the commonest metabolic disorder, diabetes pose a lethal threat to present-day sedentary human population and the concurrent disabilities afflicted with this disease. Survey reveals that it affects more than 100 million people worldwide (6% of the population) and in the next 10 years it may affect about five times the number than it does now. Since the Central Drug Research Institute, Lucknow, has an avowed objective of drug discovery and development, it is running an integral programme of screening the indigenous medicinal plants for various tropical diseases and other infectious and metabolic scourges and synthesis of biologically active natural product analogues using different synthetic methodologies. The main thrust is on the isolation and identification of a lead which through extensive biological studies could offer some promise on the clinical front. Under this programme, plants are collected from the different parts of the country and subjected to screening through a number of classic as well as modern biological tests. Exquisite bioinformatics tools are indispensably employed in arriving at an approach which could provide a rationale for targeted drug design and development. Plants showing significant activity are picked up for detailed chemical and pharmacological investigations for the identification of the active lead. Chemists are important sources for new drugs and are also good lead compounds suitable for further modification during drug development. Natural products have been the traditional pathfinder of compounds with an untold diversity of chemical structures unparalleled and unmatched even by the largest combinatorial libraries. There is a clarion calls for new antibiotics, chemotherapeutic agents and agrochemicals that are highly effective, cost-effective, possess low toxicity and have minimal side effects. The ingress to the human population of new disease causing agents such as HIV, Ebola and SARS and disorders like diabetes and dyslipidemia requires the discovery and development of new drugs to combat them. Not only do diseases like AIDS require drugs that target them specifically, but new therapies are needed for treating ancillary infections which are a consequence of a weakened immune system. In addition more drugs are needed to efficiently treat parasitic protozoan and nematodal infections such as malaria, leishmaniasis, trypanosomiasis and filariasis. Among the commonest metabolic disorder, diabetes pose a lethal threat to present-day sedentary human population and the concurrent disabilities afflicted with this disease. Survey reveals that it affects more than 100 million people worldwide (6% of the population) and in the next 10 years it may affect about five times the number than it does now. Since the Central Drug Research Institute, Lucknow, has an avowed objective of drug discovery and development, it is running an integral programme of screening the indigenous medicinal plants for various tropical diseases and other infectious and metabolic scourges and synthesis of biologically active natural product analogues using different synthetic methodologies. The main thrust is on the isolation and identification of a lead which through extensive biological studies could offer some promise on the clinical front. Under this programme, plants are collected from the different parts of the country and subjected to screening through a number of classic as well as modern biological tests. Exquisite bioinformatics tools are indispensably employed in arriving at an approach which could provide a rationale for targeted drug design and development. Plants showing significant activity are picked up for detailed chemical and pharmacological investigations for the identification of the active lead. Chemists are exploring the possibility of identifying the novel structures and synthesizing the structural analogues of identified biologically active compounds. Under the aegis of ongoing programme on drug discovery and development, phytochemical and pharmacological investigation of Indian medicinal plants and synthesis of biologically active natural products and various analogues of isolated bioactive molecules were taken up to accomplish the desired objective of the current studies. The present thesis encompasses the results and discussion of these studies and is divided into five chapters as summarized below: Chapter-1: Collates the data on the naturally occurring anti-osteoporotic agents derived from various medicinal plants with a brief overview on osteoporosis. Chapter-2: Dwells with the phytochemical and pharmacological investigation of the flowers of Pterospermum acerifolium. This includes description of plant; literature review, isolation and characterization of seventeen compounds on the basis of spectral and chemical studies. Among these, three compounds were new named as pterospermin A, pterospermin B, pterospermin C. Twelve compounds were isolated for the first time from this plant. Antiosteoporotic activity of the isolated compounds is also described. Chapter-3: This chapter deals with phytochemical investigation of the seeds of Pterospermum acerifolium. This includes isolation and characterization of ten compounds. Amongst these, eight compounds are first time reported from this plant. Biological activity of extracts is also described. Chapter-4: Presents a review on genus Dalbergia including phytoconstituents and their biological activity. Chapter-5: Describes the phytochemical and pharmacological studies of the leaves of Dalbergia sissoo. Isolation and characterization of sixteen compounds are described, out of which two compounds are new and five compounds were isolated for the first time from this plant. Antiosteoporotic activity of butanol fraction and isolated compounds are also described.