Drug discovery from natural products

Abstract

Natural product compounds are the source of numerous therapeutic agents. Recent progress to discover drugs from natural product sources has resulted in compounds that are being developed to treat cancer, resistant bacteria and viruses and immunosuppressive disorders. Many of these compounds were discovered by applying recent advances in understanding the genetics of secondary metabolism in actinomycetes, exploring the marine environment and applying new screening technologies. In many instances, the discovery of a novel natural product serves as a tool to better understand targets and pathways in the disease process. This review describes recent progress in drug discovery from natural sources including several examples of compounds that inhibit novel drug targets.

Synthesis and antimicrobial activity of dermaseptin S1 analogues

“…1 New hopes to delay the emergence and subsequent dissemination of resistant microorganisms or resistant genes come from the discovery of natural products that may act as efficient leads in the development of novel therapeutic agents. 2,3 Prominent amongst these natural products are the members of the cationic host defence peptide family, which are widely distributed in nature as a component of the immediate non-specific defence against infections. This defence peptide system exists in species of all kingdoms from insects to plants to mammals and non-mammalian vertebrates and its effectiveness has been assessed by demonstrating direct antimicrobial activity against bacteria, fungi, eukaryotic parasites and/ or viruses.…”

Future Antibiotic Agents: Turning to Nature for Inspiration

“…At Cubist Pharmaceuticals they faced the challenge by encapsulating individual environmental microbes in ~2 mm alginate macrodroplets and growing them in media favouring actinomycete growth supplemented with antibiotics against single-cell eubacteria and fungi. This technology supports the fermentation and screening of up to 10 million actinomycetes per year (Baltz, 2006;Gullo et al, 2006). Similarly, a method that couples bacterial encapsulation in gel microdroplets with flow cytometry to detect those beads that contain microcolonies was reported (Zengler et al, 2002).…”

“…Another interesting approach was reported by a team at Cubist Pharmaceuticals. They constructed a model target organism (CM400) by using E. coli engineered to harbor multiple resistance markers (conferring resistance to 16 most frequent antibiotics) (Baltz, 2006;Gullo et al, 2006). In this way, the hits are preselected to belong to new antibiotic classes.…”

The Medicinal Value of Biodiversity: New Hits to Fight Cancer

“…Finally, the studies performed until now clearly demonstrate that goniothalamin is indeed a lead compound for drug discovery from natural sources. Besides the molecules cited here, many other interesting natural products are suitable as lead compounds for the design of new drugs (Koehn & Carter, 2005;Gullo et al, 2006;Gordaliza, 2007;Lam, 2007;Molinski et al, 2009), such as curcumin, riboflavin, resveratrol, and caffeic acid (Aggarwal et al, 2003;Kaminaga et al, 2003;Aggarwal et al, 2004;de Souza et al, 2005).…”