Current strategies for drug discovery through natural products

Harvey, Alan L.; Clark, Rachel L.; Mackay, Simon P.; Johnston, Blair F.

doi:10.1517/17460441.2010.488263

Cited by 94 publications

(68 citation statements)

References 70 publications

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“…Recent comprehensive reviews of natural products, or compounds inspired by natural products, indicate that more than 100 natural product compounds are currently in clinical trials. Natural products offer the advantage of discovering novel structural classes (5,6) because of their well-documented better coverage of chemical space relative to large synthetic compounds (7). Hence, the structural or chemical diversity of natural products can be utilized to access bioactive compounds with novel scaffolds (7)(8)(9).…”

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confidence: 99%

Molecular Scaffold Analysis of Natural Products Databases in the Public Domain

2012

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Natural products represent important sources of bioactive compounds in drug discovery efforts. In this work, we compiled five natural products databases available in the public domain and performed a comprehensive chemoinformatic analysis focused on the content and diversity of the scaffolds with an overview of the diversity based on molecular fingerprints. The natural products databases were compared with each other and with a set of molecules obtained from in-house combinatorial libraries, and with a general screening commercial library. It was found that publicly available natural products databases have different scaffold diversity. In contrast to the common concept that larger libraries have the largest scaffold diversity, the largest natural products collection analyzed in this work was not the most diverse. The general screening library showed, overall, the highest scaffold diversity. However, considering the most frequent scaffolds, the general reference library was the least diverse. In general, natural products databases in the public domain showed low molecule overlap. In addition to benzene and acyclic compounds, flavones, coumarins, and flavanones were identified as the most frequent molecular scaffolds across the different natural products collections. The results of this work have direct implications in the computational and experimental screening of natural product databases for drug discovery.Key words: chemoinformatics, cyclic system, molecular diversity, natural product, Shannon entropy, Traditional Chinese Medicine.Abbreviations: CSR, cumulative scaffold recovery; MACCS, Molecular ACCess System; MEQI, Molecular Equivalence Index; MOE, molecular operating environment; SE, Shannon entropy; TCM, Traditional Chinese Medicine.Received 22 June 2012, revised 18 July 2012 and accepted for publication 19 July 2012Traditionally, natural products have played a major role in drug discovery and development by providing novel chemical scaffolds, and serving as leads or drugs (1,2). For many years, 80% of drugs were either natural products or natural product-derived compounds. Even in the modern era, after the advent of techniques such as high-throughput screening of synthetic libraries, half of the drugs approved since 1994 are based on natural products research (3,4). Recent comprehensive reviews of natural products, or compounds inspired by natural products, indicate that more than 100 natural product compounds are currently in clinical trials. Natural products offer the advantage of discovering novel structural classes (5,6) because of their well-documented better coverage of chemical space relative to large synthetic compounds (7). Hence, the structural or chemical diversity of natural products can be utilized to access bioactive compounds with novel scaffolds (7-9). The inclusion of sources of natural products in drug discovery would open up more avenues for new classes of drugs (10) as well as new chemical entities, evidenced by studies that show structural or chemical complementarity between natural...

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confidence: 99%

Molecular Scaffold Analysis of Natural Products Databases in the Public Domain

2012

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“…Furthermore, the wide spectrum of therapeutic activity makes the natural products attractive candidates for further research (Vlietinck & Van Den Berghe, 1991). In this context, a new recognition has been given to ethnopharmacology, traditional, complementary and alternative medicines, which re-emerging as new strategic options in health attention, has provided valuable clues of plants with bioactive compounds potentially usable in the production of new drugs (Harvey et al, 2010;Patwardhan & Vaidyab, 2010). The World Health Organization's Commission on Intellectual Property and Innovation in Public Health also has duly recognized the promise and role of traditional medicine in developing affordable drugs for the treatment of health problems (Patwardhan, 2005a;Patwardhan & Vaidyab, 2010).…”

Section: Contribution Of Ethnopharmacology In the Selection Of Naturamentioning

confidence: 99%

“…Furthermore, the use of plants and their phytoconstituents in the treatment of gastrointestinal diseases is promising due to the broad spectrum of action on various defensive mechanisms like antioxidant, antinflamatory, imunomodulatory, cytoprotective and antisecretory (Newall et al, 1996). Although several plants have showed beneficial gastroprotective effects, earlier publications, and researchers from around the world, have pointed out that relatively little of the world's plant biodiversity has been extensively screened for bioactivity (Harvey et al, 2010), and this scenario extends to most plants that have traditional indication for the management of gastric ulcers.…”

Section: Peptic Ulcers and Herbal Medicinementioning

confidence: 99%

“…Also, studies on cabbage, previously employed as an anti-ulcer agent in folk medicine, has led to the development of gefarnate, a drug used for the treatment of gastric ulcers (Akhtar & Munir, 1989). Thus, a search among medicinal plants is still important, despite the progress in conventional chemistry and pharmacology in producing effective drugs (Harvey et al, 2010 Important questions related with crude drugs are the necessary amount of plant part to provide a healing response, traditional way of preparation (infusion, decoction and maceration), concentration (plant/solvent ratio), frequency and duration of treatment. Unfortunately, this basic information is not always present in ethnopharmacological studies and this fact is surprising as there should be a realistic approach to the doses to confirm the reputed effectiveness of the crude drugs.…”

Section: Ethnopharmacological Discovery Of Antiulcer Crude Drugsmentioning

confidence: 99%

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Ethnopharmacology as Current Strategy in the Search of Novel Anti-Ulcerogenic Drugs: Case of a Brazilian Medicinal Plant (Maytenus ilicifolia Mart. ex. Reissek)

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2011

Peptic Ulcer Disease

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“…Because chemists can only enter compounds into the Portal's database if they can guarantee that they can supply the compounds and because biologists can only suggest targets if they have relevant assays available, the reduction to practice can be very rapid after the initial in silico screening. The unique chemical database is rapidly expanding (currently over 14,500 compounds), with academic scientists from 21 institutions in five continents contributing, and the compounds have been shown to be highly diverse but still generally drug-like in their properties Harvey et al, 2010;Schuster & Wolber, 2010). Another approach to using natural products and virtual screening has been developed at the University of Innsbruck, Austria.…”

Section: Current Practices In Bioprospectingmentioning

confidence: 99%