title: Chemistry and biology of fascaplysin, a potent marine-derived CDK-4 inhibitor.
abstract: Marine natural products offer an abundant source of pharmacologically active agents with great diversity and complexity, and the potential to produce valuable therapeutic entities. Indole alkaloids is one of the important class of marine-derived secondary metabolites, with wide occurrence amongst variety of marine sources such as sponges, tunicates, algae, worms and microorganisms and have been extensively studied for their biological activities. Among this chemical family, a sponge-derived bis-indole alkaloid fascaplysin (1) exhibited broad range of bioactivities including antibacterial, antifungal, antiviral, anti-HIV-1-RTase, p56 tyrosine kinase inhibition, antimalarial, anti-angiogenic, antiproliferative activity against numerous cancer cell lines, specific inhibition of cyclin-dependent kinase-4 (IC(50) 350 nM) and action as a DNA intercalator. In the present review, the chemical diversity of natural as well as synthetic analogues of fascaplysin has been reviewed with a detailed account on synthetic reports and pharmacological studies. Our analysis of the structure-activity relationships of this family of compounds highlights the existence of various potential leads for the development of novel anticancer agents.
authors.affiliation: Scientist, Medicinal Chemistry Division, Indian Institute of Integrative Medicine, Jammu, India. sbharate@iiim.ac.in
authors.forename: S B
authors.initials: SB
authors.lastname: Bharate
authors.forename: S
authors.initials: S
authors.lastname: Manda
authors.forename: N
authors.initials: N
authors.lastname: Mupparapu
authors.forename: N
authors.initials: N
authors.lastname: Battini
authors.forename: R A
authors.initials: RA
authors.lastname: Vishwakarma
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D059001:Aquatic Organisms / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013379:Substrate Specificity; D000644:Quaternary Ammonium Compounds; D002243:Carbolines; D007212:Indolizines
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D051358:Cyclin-Dependent Kinase 4; D007211:Indoles; D047428:Protein Kinase Inhibitors; C069346:fascaplysine; D000644:Quaternary Ammonium Compounds; D002243:Carbolines; D007212:Indolizines