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

Shibo Jiang, Srinivasa R. Tala, Hong Lu, Peng Zou, Ilker Avan, Tarek S. Ibrahim, Nader E. Abo-Dya, Abdelmotaal Abdelmajeid, Asim K. Debnath, Alan R. Katritzky

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6895-6898
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number22
DOIs
StatePublished - Nov 15 2011

Keywords

  • ELISA
  • Furans
  • Gp41
  • HIV-1 fusion inhibitors
  • Pyrroles

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    Jiang, S., Tala, S. R., Lu, H., Zou, P., Avan, I., Ibrahim, T. S., Abo-Dya, N. E., Abdelmajeid, A., Debnath, A. K., & Katritzky, A. R. (2011). Design, synthesis, and biological activity of a novel series of 2,5-disubstituted furans/pyrroles as HIV-1 fusion inhibitors targeting gp41. Bioorganic and Medicinal Chemistry Letters, 21(22), 6895-6898. https://doi.org/10.1016/j.bmcl.2011.08.081