Natural products have contributed to the development of many drugs for diverse indications. While most U.S. pharmaceutical companies have reduced or eliminated their in-house natural product groups, new paradigms and new enterprises have evolved to carry on a role for natural products in the pharmaceutical industry. Many of the reasons for the decline in popularity of natural products are being addressed by the development of new techniques for screening and production. This overview aims to inform pharmacologists of current strategies and techniques that make natural products a viable strategic choice for inclusion in drug discovery programs.Keywords natural products; drugs discovery; HTS 1. History
Early natural product drugsHumans have long used naturally occurring substances for medical purposes. Plants, in particular, have played a leading medical role in most cultures. With the development of the science of chemistry at the beginning of the 19 th century, plants began to be examined more closely to understand why they were medically useful. In 1804 Sertürner purified morphine from opium and found that it largely reproduced the analgesic and sedative effects of opium. (Lockemann, 1951) His success led others to seek "active principles" of medicinal plants, and throughout the century, bioactive pure natural products were found in cinchona (quinine) (Borchardt, 1996), coca (cocaine) (Gay et al., 1975), and many other plants. The ability to determine the structure of these compounds developed more slowly, with morphine's planar structure determined in 1923 (Gulland and Robinson, 1923), quinine's structure elucidated in 1908 (Rabe, 1908) and cocaine in 1898 (Willstätter and Müller, 1898). The ability to synthesize these compounds took longer yet, for example, morphine was first synthesized in 1956 (Gates and Tschudi, 1956). While the active principle approach has not been a universal explanation for all biological activities of natural substances, it remains the most productive hypothesis.
The antibiotic eraThe identification of penicillin's antibacterial activity by Fleming (Fleming, 1929) and its isolation by Chain and Florey (Chain et al., 1940) revolutionized medicine and led to extensive screening of microbes, particularly soil actinomycetes and fungi, to identify other antibiotic compounds. Using simple bioassays, microbes from soil samples were cultured, identified, and dozens of classes of antibiotics were isolated and elucidated; many of them were commercialized and are still used in clinical practice (Wenzel, 2004). While the evolution of drug resistance in clinically important infections has limited the use of many natural antibiotics, their discovery and commercialization laid the scientific and financial foundation of the modern pharmaceutical industry after World War II.
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Author ManuscriptCurr Protoc Pharmacol. Author manuscript; available in PMC 2010 September 1. Wani et al., 1971) and camptothecin analogs (Lerchen, 2002;Wani and Wall, 1969) were the most prominent devel...