Multi-step synthesis of indole-N-ethyltriazole hybrids amalgamated with N-arylated ethanamides: structure-activity relationship and mechanistic explorations through tyrosinase inhibition, kinetics and computational ascriptions

• Designing of indole- N -ethyltriazole hybrids amalgamated with N -arylated ethanamides as tyrosinase inhibitors • Ascertaining of in vitro inhibitory potential, kinetics and structure-activity relationships • In silico computational studies to augment the in vitro results • Exploration of these multi-functional hybrid molecules against tyrosinase to obtain better and safe therapeutic agents for skin pigmentation and related ailments. In the study presented here, novel bioactive series of indole- N -ethyltriazole hybrids was synthesized and structures of these hybrid molecules ( 9a-h ) were corroborated by IR, 1 H-NMR, 13 C-NMR, EI-MS and CHN analysis data. The in vitro studies of these multi-functional molecules demonstrated their potent tyrosinase inhibition relative to the standard used and all the synthesized compounds showed mild hemolysis. The kinetics mechanism was exposed by lineweaver-burk plots which revealed that, 9c , inhibited tyrosinase non-competitively by forming an enzyme-inhibitor complex. So, it was summated that these hybrid molecules might lead to further research gateways for obtaining better and safe therapeutic agents for skin pigmentation and related ailments.