Synthesis and anti-HIV activity of alkylated quinoline 2,4-diols

Nafees Ahmed, Keyur G. Brahmbhatt, Sudeep Sabde, Debashis Mitra, Inder Pal Singh, Kamlesh K. Bhutani

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128 Citations (Scopus)

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-1NL4.3 virus by p24 antigen capture ELISA assay. The compounds 1 and 2 showed potent inhibitory activity with IC50 value of 2.99 and 3.80 μM, 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 IC50 value of 2.35 μM 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 CC50 values which indicate that they have better therapeutic indices.

Original languageEnglish
Pages (from-to)2872-2879
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number8
DOIs
Publication statusPublished - 15 Apr 2010
Externally publishedYes

Keywords

  • Alkylation
  • Anti-HIV activity
  • CEM-GFP cells
  • Quinoline 2,4-diol

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