Design, synthesis, and biological activity of a novel series of 2,5-disubstituted furans/pyrroles as HIV-1 fusion inhibitors targeting gp41

Jiang S., Tala S. R., Lu H., Zou P., Avan I., Ibrahim T. S., ...More

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol.21, no.22, pp.6895-6898, 2011 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 21 Issue: 22
  • Publication Date: 2011
  • Doi Number: 10.1016/j.bmcl.2011.08.081
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.6895-6898
  • Keywords: HIV-1 fusion inhibitors, Gp41, Furans, Pyrroles, ELISA, ENTRY INHIBITORS
  • Anadolu University Affiliated: Yes


Based on molecular docking analysis of earlier results, we designed a series of 2,5-disubstituted furans/pyrroles (5a-h) as HIV-1 entry inhibitors. Compounds were synthesized by Suzuki-Miyaura cross coupling, followed by a Knoevenagel condensation or Wittig reaction. Four of these compounds were found to be effective in inhibiting HIV-1 infection, with the best compounds being 5f and 5h, which exhibited significant inhibition on HIV-1(IIIB) infection at micromolar levels with low cytotoxicity. These compounds are also effective in blocking HIV-1 mediated cell-cell fusion and the gp41 six-helix bundle formation, suggesting that they are also HIV-1 fusion inhibitors targeting gp41 and have potential to be developed as a new class of anti-HIV-1 agents. (C) 2011 Elsevier Ltd. All rights reserved.