title: Anti-HIV activity of semisynthetic derivatives of andrographolide and computational study of HIV-1 gp120 protein binding.
abstract: Andrographolide, a diterpene lactone of the Andrographis paniculata, displays anti-HIV activity in vitro. A series of andrographolide derivatives have been synthesized and evaluated for their anti-HIV activity in a cell-free virus infectivity assay using TZM-bl cells. As compared to andrographolide, 3-nitrobenzylidene derivative 6 showed higher in vitro anti-HIV activity, whereas 2',6'-dichloro-nicotinoyl ester derivative 9 showed higher Therapeutic Index. The andrographolide and its derivatives, 6 and 9, inhibited gp120-mediated cell fusion of HL2/3 cells (expressing gp120 on its surface) with TZM-bl cells (expressing CD4 and co-receptors CCR5 & CXCR4). Further, computational studies revealed that these molecules bind to the important residues of V3 loop of gp120. These results suggest that andrographolide derivatives may be promising candidates for prevention of HIV infection.
authors.affiliation: Laboratory for Advanced Research in Natural and Synthetic Chemistry, V. G. Vaze College, Mumbai University, Mithagar Road, Mulund (East), Mumbai 400 081, India.
authors.forename: Mayur M
authors.initials: MM
authors.lastname: Uttekar
authors.forename: Tiyasa
authors.initials: T
authors.lastname: Das
authors.forename: Rohan S
authors.initials: RS
authors.lastname: Pawar
authors.forename: Beena
authors.initials: B
authors.lastname: Bhandari
authors.forename: Vidya
authors.initials: V
authors.lastname: Menon
authors.lastname: Nutan
authors.forename: Satish K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Sujata V
authors.initials: SV
authors.lastname: Bhat
mesh_terms: D035685:Andrographis / Q000737:chemistry; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D004224:Diterpenes; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1; C030419:andrographolide