title: Design, synthesis, and biological activity of a novel series of 2,5-disubstituted furans/pyrroles as HIV-1 fusion inhibitors targeting gp41.
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.
authors: Lindsley F. Kimball Research Institute, New York Blood Center, NY 10065, USA. sjiang@nybloodcenter.org
authors: Shibo
authors: S
authors: Jiang
authors: Srinivasa R
authors: SR
authors: Tala
authors: Hong
authors: H
authors: Lu
authors: Peng
authors: P
authors: Zou
authors: Ilker
authors: I
authors: Avan
authors: Tarek S
authors: TS
authors: Ibrahim
authors: Nader E
authors: NE
authors: Abo-Dya
authors: Abdelmotaal
authors: A
authors: Abdelmajeid
authors: Asim K
authors: AK
authors: Debnath
authors: Alan R
authors: AR
authors: Katritzky
mesh_terms: D015195:Drug Design; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023581:HIV Fusion Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D005663:Furans; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D011758:Pyrroles