title: Discovery of novel low-molecular-weight HIV-1 inhibitors interacting with cyclophilin A using in silico screening and biological evaluations.
abstract: Cyclophilin A has attracted attention recently as a new target of anti-human immunodeficiency virus type 1 (HIV-1) drugs. However, so far no drug against HIV-1 infection exhibiting this mechanism of action has been approved. To identify new potent candidates for inhibitors, we performed in silico screening of a commercial database of more than 1,300 drug-like compounds by using receptor-based docking studies. The candidates selected from docking studies were subsequently tested using biological assays to assess anti-HIV activities. As a result, two compounds were identified as the most active. Specifically, both exhibited anti-HIV activity against viral replication at a low concentration and relatively low cytotoxicity at the effective concentration inhibiting viral growth by 50%. Further modification of these molecules may lead to the elucidation of potent inhibitors of HIV-1.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yu-Shi
authors.initials: YS
authors.lastname: Tian
authors.forename: Chris
authors.initials: C
authors.lastname: Verathamjamras
authors.forename: Norihito
authors.initials: N
authors.lastname: Kawashita
authors.forename: Kousuke
authors.initials: K
authors.lastname: Okamoto
authors.forename: Teruo
authors.initials: T
authors.lastname: Yasunaga
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ikuta
authors.forename: Masanori
authors.initials: M
authors.lastname: Kameoka
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takagi
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D021984:Cyclophilin A / Q000378:metabolism*; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D008970:Molecular Weight; D013816:Thermodynamics; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D008024:Ligands; D021984:Cyclophilin A