The Role of Natural Product Chemistry in Drug Discovery

Abstract

Although traditionally natural products have played an important role in drug discovery, in the past few years most Big Pharma companies have either terminated or considerably scaled down their natural product operations. This is despite a significant number of natural product-derived drugs being ranked in the top 35 worldwide selling ethical drugs in 2000, 2001, and 2002. There were 15 new natural product-derived drugs launched from 2000 to 2003, as well as 15 natural product-derived compounds in Phase III clinical trials or registration at the end of 2003. Recently, there has been a renewed interest in natural product research due to the failure of alternative drug discovery methods to deliver many lead compounds in key therapeutic areas such as immunosuppression, anti-infectives, and metabolic diseases. To continue to be competitive with other drug discovery methods, natural product research needs to continually improve the speed of the screening, isolation, and structure elucidation processes, as well addressing the suitability of screens for natural product extracts and dealing with issues involved with large-scale compound supply.

Isolation and antitrichomonal activity of the chemical constituents of the leaves of Maytenus phyllanthoides Benth. (Celastraceae)

“…Chromatography of fraction G over Sephadex LH-20 afforded 36 fractions that, after a TLC analysis, were combined in eight fractions (1)(2)(3)(4)(5)(6)(7)(8). Fraction G8 chromatographed on silica gel 60 (37-74 mm) eluted with a mixture of hexane-ethyl acetate of increasing polarity.…”

“…Fifty-six fractions were obtained and combined into 10 fractions. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Lupeol (6 mg) and oleanolic acid (3 mg) were obtained from fraction G8g7 after purification by TLC where they eluted with CHCl 3 -EtOAc (98:2).…”

“…6 It is well known that natural products could be a source of potent and selective drugs. 7 In this context, plants of the Maytenus genus (Celastraceae) are known to produce several bioactive compounds, including antiprotozoal compounds. 8 This genus is widely distributed around the world mainly in the tropics and subtropics.…”

Biologia química: uma estratégia moderna para a pesquisa em produtos naturais

“…A importância dos produtos naturais na descoberta e desenvolvimento de fármacos é bem documentada 5,15,16 , estando a pesquisa nesta área inserida tanto no segundo quanto no terceiro desafio da Biologia Química. Apesar dos progressos nas técnicas de sequenciamento de vários genomas, do acesso aos compostos diversificados de coleções combinatórias, do planejamento racional baseados nas estruturas de proteínas puras, dos ensaios em larga escala (high-throughput screening, HTS) e dos métodos computacionais, observou-se uma queda de produtividade na indústria farmacêutica justamente durante um período de dramático crescimento e investimentos em pesquisa e desenvolvimento 17 .…”

“…As novas tecnologias introduzidas para a descoberta e desenvolvimento de fármacos, como química combinatória e HTS, não tiveram o impacto esperado na produtividade, apesar das vantagens de serem mais rápidas e de menor custo, além de definirem de forma clara a propriedade intelectual 19 . A química cominatória, por exemplo, foi responsável pelo surgimento de apenas uma nova entidade química de domínio público, o agente antitumoral sorafenibe (Nexavar, Bayer), aprovada pelo FDA em 2005 5 , enquanto os produtos naturais contribuíram de forma mais significativa para o desenvolvimento de vários fármacos originais 5,15,16 .…”