Synthesis of Novel 3-(5-(Alkyl/arylthio)-1,3,4-Oxadiazol-2-yl)-8-Phenylquinolin-4(1<i>H</i>)-One Derivatives as Anti-HIV Agents

<p>Novel quinolone derivatives featuring an 1,3,4-oxadiazole ring as a metal-chelating component and a benzyl group base on HIV-1 integrase inhibitors pharmacophore were designed and synthesized. An antiviral assay revealed that most analogues inhibited HIV-1 replication in the cell culture. Our results showed that compounds bearing small alkyl groups as R group were inactive in anti-HIV-1 assay, whereas compounds possessing benzyl or substituted benzyl at the same position showed good anti-HIV activity with the range of 20–57% at 100 μM concentration. Among them, 3-(5-((2-fluorobenzyl)thio)-1,3,4-oxadiazol-2-yl)-8-phenylquinolin-4-(1<i>H</i>)-one (compound <b>13</b>) showed reasonable cell-based antiviral activity (EC<sub>50</sub> = 50 μM) with no considerable cytotoxicity (CC<sub>50</sub> > 100 μM) in the cell viability assay, suggesting that it may be amenable to further development for identifying new anti-HIV-1 agents. Docking studies using the later crystallographic data available for PFV integrase corroborate favorable binding to the active site of HIV integrase, providing a basis for the design of more potent analogues.</p>