title: Synthesis and anti-HIV activity of alkylated quinoline 2,4-diols.
abstract: Naturally occurring quinolone alkaloids, buchapine (1) and compound 2 were synthesized as reported in literature and evaluated for anti-HIV potential in human CD4+ T cell line CEM-GFP, infected with HIV-1(NL4.3) virus by p24 antigen capture ELISA assay. The compounds 1 and 2 showed potent inhibitory activity with IC(50) value of 2.99 and 3.80microM, respectively. Further, 45 alkylated derivatives of quinoline 2,4-diol were synthesized and tested for anti-HIV potential in human CD4+ T cell line CEM-GFP. Among these, 13 derivatives have shown more than 60% inhibition. We have identified three most potent inhibitors 6, 9 and 23; compound 6 was found to be more potent than lead molecule 1 with IC(50) value of 2.35microM and had better therapeutic index (26.64) as compared to AZT (23.07). Five derivatives 7, 19a, 19d, 21 and 24 have displayed good noticeable anti-HIV activity. All active compounds showed higher CC(50) values which indicate that they have better therapeutic indices.
authors.affiliation: Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali 160062 Punjab, India.
authors.forename: Nafees
authors.initials: N
authors.lastname: Ahmed
authors.forename: Keyur G
authors.initials: KG
authors.lastname: Brahmbhatt
authors.forename: Sudeep
authors.initials: S
authors.lastname: Sabde
authors.forename: Debashis
authors.initials: D
authors.lastname: Mitra
authors.forename: Inder Pal
authors.initials: IP
authors.lastname: Singh
authors.forename: Kamlesh K
authors.initials: KK
authors.lastname: Bhutani
mesh_terms: D000478:Alkylation; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D011804:Quinolines