title: Computer-aided design, synthesis, and biological activity evaluation of potent fusion inhibitors targeting HIV-1 gp41.
abstract: This discovered and optimized several novel HIV-1 fusion inhibitors and further evaluated the inhibitory activities of these compounds in vitro. Here, we have reported the computer-aided design, synthesis, and biological evaluation of a series of small molecule fusion inhibitors targeting HIV-1 gp41. Based on the structure of inhibitor (NB2), we carried out de novo design and screened out a series of novel structure molecules by using Leapfrog and Autodock programs. Our structure-based modification obtained a potent fusion inhibitor (IC₅₀ = 41.1 µg/mL). Several novel compounds were discovered as fusion inhibitors, which suggested that our design methodology is reliable, paving the way for de novo design of novel small-molecule HIV inhibitors targeting gp41.
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Jian Jun
authors.initials: JJ
authors.lastname: Tan
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Xiao Jing
authors.initials: XJ
authors.lastname: Cong
authors.forename: Lei Fu
authors.initials: LF
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Ren
authors.initials: R
authors.lastname: Kong
authors.forename: Zhi Yao
authors.initials: ZY
authors.lastname: Kui
authors.forename: Cun Xin
authors.initials: CX
authors.lastname: Wang
authors.forename: Li Ming
authors.initials: LM
authors.lastname: Hu
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001565:Benzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017076:Computer-Aided Design; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; 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; D062385:Hydroxybenzoates; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C568547:4-(3-benzoyl-2-methyl-5-phenyl-1H-pyrrol-1-yl)-2-hydroxybenzoic Acid; D019380:Anti-HIV Agents; D001565:Benzoates; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D062385:Hydroxybenzoates; D011758:Pyrroles