Design, synthesis and computational studies of N-(substituted-phenyl)-4-(4-phenyl-1-piperazinyl)butanamides as potent anti-melanogenic and tyrosinase inhibitors

This manuscript describes the synthesis of some new N-(substituted-phenyl)-4-(4-phenyl-1-piperazinyl) butanamides (5a-c) through a facile bi-step strategy. The structures of these compounds were corroborated by their IR, EI-MS, H-1 NMR, C-13 NMR spectra along with CHN analysis data. The results of Mushroom tyrosinase in vitro inhibition revealed that all compounds were superb inhibitors of this enzyme and among them 5b was identified as the most active compound having IC50 value of 0.168 +/- 0.057 mu M, relative to the standard (16.841 +/- 1.146 mu M). The kinetic analysis (K-i = 0.22 mu M) of this molecule revealed that it does not competitively inhibit the tyrosinase enzyme. It also significantly reduced (P < 0.001) the enormous amount of pigments to about 75.373% in an in vivo protocol, when studied on the zebrafish embryos. Moreover, the cytotoxicity of these butanamides was also profiled and it was an inferred that of these molecules possess very mild cytotoxicity. So, it was consummated from the present investigation that these compounds might be utilized as less cytotoxic therapeutic agents for the betterment of skin related ailments. (C) 2020 Published by Elsevier B.V.