Combining molecular docking and QSAR studies for modeling the anti-tyrosinase activity of aromatic heterocycle thiosemicarbazone, analogues

A collection of thirty-six aromatic heterocycle thiosemicarbazone analogues presented a broad span of anti-tyrosinase activities were designed and obtained. A robust and reliable two-dimensional quantitative structure-activity relationship model, as evidenced by the high q(2) and r(2) values (0.848 and 0.893, respectively), was gained based on the analogues to predict the quantitative chemical-biological relationship and the new modifier direction. Inhibitory activities of the compounds were found to greatly depend on molecular shape and orbital energy. Substituents brought out large ovality and high highest-occupied molecular orbital energy values helped to improve the activity of these analogues. The molecular docking results provided visual evidence for QSAR analysis and inhibition mechanism. Based on these, two novel tyrosinase inhibitors 004 and 005 with predicted IC50 of 0.5384 and 0.8752 nM were designed and suggested for further research. (C) 2017 Published by Elsevier B.V.