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The Success of Natural Products in Drug Discovery

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The Success of Natural Products in Drug Discovery Pharmacology & Pharmacy, 2013, 4, 17-31 17 http://dx.doi.org/10.4236/pp.2013.43A003 Published Online June 2013 (http://www.scirp.org/journal/pp) The Success of Natural Products in Drug Discovery Mouhssen Lahlou Service des Sciences de la Vie, Ministère de l’Enseignement Supérieur, de la Recherche Scientifique et de la Formation des Cadres, Rabat, Morocco. Email: [email protected] Received April 25th, 2013; revised May 27th, 2013; accepted June 5th, 2013 Copyright © 2013 Mouhssen Lahlou. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Drug discovery leading to robust and viable lead candidates’ remains a challenging scientific task, which is the transi- tion from a screening hit to a drug candidate, requires expertise and experience. Natural products and their derivatives have been recognized for many years as a source of therapeutic agents and of structural diversity. However, in addition to their chemical structure diversity and their biodiversity, the development of new technologies has revolutionized the screening of natural products in discovering new drugs. Applying these technologies compensates for the inherent limi- tations of natural products and offers a unique opportunity to re-establish natural products as a major source for drug discovery. The present article attempts to describe the utilization of compounds derived from natural resources as drug candidates, with a focus on the success of these resources in the process of finding and discovering new and effective drug compounds, an approach commonly referred to as “natural product drug discovery”. Keywords: Biodiversity; Drug Discovery; Efficacy; Natural Products; New Technologies; Structural and Chemical Diversity; Success Steps 1. Introduction lated chemicals, instead of extracts, became the standard treatments for diseases. Indeed, many bioactive com- Natural products, including plants, animals and minerals pounds, responsible for the effects of crude extract drugs, have been the basis of treatment of human diseases [1,2]. and their chemical structure was elucidated. Nevertheless, ancient wisdom has been the basis of mod- Classical examples of drug compounds discovered this ern medicine and will remain as one important source of way are morphine, the active agent in Opium, and future medicine and therapeutics. digoxin, a heart stimulant originating from flower Digi- History of medicine dates back practically to the exis- talis lanata. The evolution in synthetic chemistry also led tence of human civilization. Historically, the majority of to chemical synthesis of many of the elucidated struc- new drugs have been generated from natural products tures. (secondary metabolites) and from compounds derived On the other hand, the R&D thrust in the pharmaceu- from natural products [1]. tical sector is focused on development of new drugs, in- Before 20th century, crude and semi-pure extracts of novative/indigenous processes for known drugs and de- plants, animals, microbes and minerals represented the velopment of plant-based drugs through investigation of only medications available to treat human and domestic leads from the traditional systems of medicine [2]. The animal illnesses. The 20th century revolutionized the exploitation of structural chemical databases consisting thinking in the use of drugs, as the receptor theory of of a wide variety of chemotypes, in conjunction with drug action. The idea that effect of drug in human body databases on target genes and proteins, will surely facili- are mediated by specific interactions of the drug mole- tate the creation of new chemical entities through com- cule with biological macromolecules (proteins or nucleic putational molecular modeling for pharmacological acids in most cases) led scientist to the conclusion that evaluation [3]. individual chemical compounds in extracts, rather than Recently, there has been a renewed interest in natural some mystical “power of life” are the factors required for product research due to the failure of alternative drug the biological activity of the drug. This lead to the begin- discovery methods to deliver many lead compounds in ning of a totally new era in pharmacology, as pure, iso- key therapeutic areas such as immunosuppression, anti- Copyright © 2013 SciRes. PP 18 The Success of Natural Products in Drug Discovery infectives, and metabolic diseases. contribute significantly to the profitability of many com- Natural products research continues to explore a vari- panies. ety of lead structures, which may be used as templates Natural products research continues to explore a vari- for the development of new drugs by the pharmaceutical ety of lead structures, which may be used as templates industry. There is no doubt that natural products have for the development of new drugs by the pharmaceutical been, and will be, important sources of new pharmaceu- industry [2]. These approved substances, representative tical compounds [1]. of very wide chemical diversity, continue to demonstrate Although traditionally natural products have played an the importance of compounds from natural sources in important role in drug discovery, in the past few years modern drug discovery efforts [6]. most Big Pharma companies have either terminated or In addition, natural products, containing inherently considerably scaled down their natural product opera- large-scale structural diversity than synthetic compounds, tions. This is despite a significant number of natural have been the major resources of bioactive agents and product-derived drugs being ranked worldwide selling will continually play as protagonists for discovering new ethical drugs in the last years. The process in natural drugs [7]. Drug discovery from medicinal plants has product drug discovery usually required several separa- mainly relied on biological activity guided isolation tion circles and structure elucidation and was thus time- methods which have led to the discovery of important consuming. drugs [1]. New approaches to improve and accelerate the joint The place of natural products in the therapeutic arsenal drug discovery and development process are expected to was rigorously discussed and analyzed [1]. A natural take place mainly from innovation in drug target elucida- product is a chemical compound or substance produced tion and lead structure discovery. Powerful new tech- by a living organism-found in nature that usually has a nologies such as automated separation techniques, high- pharmacological or biological activity for use in phar- throughput screening and combinatorial chemistry are maceutical drug discovery and drug design. This product revolutionizing drug discovery [2]. can be considered as such even if it can be prepared by The present paper discusses and examines how natural total synthesis. It’s may be extracted from tissues of ter- products have produced successful results for the phar- restrial plants, marine organisms or microorganism fer- maceutical industry for drug discovery and development, mentation broths. A crude (untreated) extract from any and why nature still remains as important source of new one of these sources typically contains novel, structurally drug compounds until today. It’s also offers a broad diverse chemical compounds. overview of the newest techniques being used in phar- Not all natural products can be fully synthesized and maceutical research today for drug discovery. many natural products have very complex structures that are too difficult and expensive to synthesize on an indus- 2. Nature as Source of New Drug trial scale. These include drugs such as penicillin, mor- Compounds phine, and formerly paclitaxel. Such compounds can only Natural products have played a key role in pharma re- be harvested from their natural source—a process which search, as many medicines are either natural products or can be tedious, time consuming, and expensive, as well derivatives thereof. Indeed, it is estimated that about 40% as being potentially unsustainable for the resource. Fur- of all medicines is either natural products or their semi- thermore, the number of structural analogues that can be synthetic derivatives [4]. obtained from harvesting is severely limited. Clinical, pharmacological, and chemical studies of A further problem is that isolates often work differ- these traditional medicines, which were derived predomi- ently than the original natural products which have syn- nantly from plants, were the basis of most early medi- ergies and may combine, say, antimicrobial compounds cines such as aspirin, digitoxin, morphine, quinine, and with compounds that stimulate various pathways of the pilocarpine [5]. immune system. Despite competition from other drug discovery meth- Many higher plants contain novel metabolites with dif- ods, natural products are still providing their fair share of ferent biological properties. However, in the developed new clinical candidates and drugs [5]. These compounds world almost all clinically used chemotherapeutics have were still a significant source of new drugs, especially in been produced by in vitro chemical synthesis. Excep- the anticancer, antihypertensive, anti-infectives, immuno- tions, like taxol and vincristine, were structurally com- suppression, and neurological disease therapeutic areas, plex metabolites that were difficult to synthesize in vitro. and some of them have since
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