Specificity in the interaction of natural products with their target proteins--a biochemical and structural insight.
Natural products are an abundant source of anti cancer agents. They act as cytotoxic drugs, and inhibitors of apoptosis, transcription, cell proliferation and angiogenesis. While pathways targeted by natural products have been well studied, there is paucity of information about the in vivo molecular target/s of these compounds. This review summarizes some of the natural compounds for which the molecular targets, mechanism of action and structural basis of specificity have been well documented. These examples illustrate that 'off target' binding can be explained on the basis of diversity inherent to biomolecular interactions. There is enough evidence to suggest that natural compounds are potent and versatile warheads that can be optimized for a multi targeted therapeutic intervention in cancer.
Venkatraman
Prasanna
P
Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, KS 137, Sector 22, Kharghar, Navi Mumbai, Maharashtra 410210, India. vprasanna@actrec.gov.in
D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001549:Benzamides; D001688:Biological Products / Q000627:therapeutic use*; D003510:Cyclohexanes / Q000627:therapeutic use; D004852:Epoxy Compounds / Q000627:therapeutic use; D005231:Fatty Acids, Unsaturated / Q000627:therapeutic use; D005419:Flavonoids / Q000627:therapeutic use; D006801:Humans; D000068877:Imatinib Mesylate; D018942:Macrolides / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy; D010879:Piperazines / Q000737:chemistry / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001549:Benzamides; D001688:Biological Products; D003510:Cyclohexanes; D004852:Epoxy Compounds; D005231:Fatty Acids, Unsaturated; D005419:Flavonoids; D018942:Macrolides; D010879:Piperazines; D010880:Piperidines; D011506:Proteins; D011743:Pyrimidines; D012717:Sesquiterpenes; C522342:pladienolide B; C077990:alvocidib; C026211:fumagillin; D000068877:Imatinib Mesylate