Isoindolin-1-one derivatives as urease inhibitors: Design, synthesis, biological evaluation, molecular docking and in-silico ADME evaluation.

An efficient, one-pot and four-component protocol for the synthesis of new series of 2,3-disubstituted isoindolin-1-ones is performed and their Jack bean urease inhibitory activities are evaluated. All the obtained compounds 5a-p were found to be more active than the standard drugs thiourea and hydroxyurea. Molecular docking studies of these compounds were also performed that verified the results form in vitro tests. • Isoindolin-1-ones as new urease inhibitors. • Docking studies and in-silico ADME evaluation of derivatives. An efficient, one-pot and four-component synthesis of a new series of 2,3-disubstituted isoindolin-1-ones is described and their Jack bean urease inhibitory activities are evaluated. Heating a mixture of 1,1-bis(methylthio)-2-nitroethene, a 1,2-diamine, a 2-formylbenzoic acid and a primary amine in EtOH for 3.5 h afforded the corresponding 2,3-disubstituted isoindolin-1-ones in good to excellent yields. All sixteen synthesized isoindolin-1-one derivatives 5a–p showed urease inhibitory activity. Among them, 5c showed the most urease inhibitory activity (IC 50 = 10.07 ± 0.28 µM) being over 2-fold more potent than thiourea (IC 50 = 22.01 ± 0.10 µM) and 10-fold than hydroxyurea (IC 50 = 100.00 ± 0.02 µM) as the standard inhibitors, respectively. Also, results from molecular docking studies were in good agreement with those obtained from in vitro tests. [ABSTRACT FROM AUTHOR]