Synthesis of Bi-heterocyclic Sulfonamides as Tyrosinase Inhibitors: Lineweaver–Burk Plot Evaluation and Computational Ascriptions

Abstract

The designed bi-heterocyclic sulfonamides were synthesized through a two-step protocol and their structures were ascertained by spectral techniques including IR, 1H NMR and 13C NMR along with CHN analysis. The in vitro inhibitory effects of these sulfonamides were evaluated against tyrosinase and kinetics mechanism was analyzed by Lineweaver–Burk plots. The binding modes of these molecules were ascribed through molecular docking studies. These synthesized bi-heterocyclic molecules were identified as potent inhibitors relative to the standard (kojic acid) and compound 5 inhibited the tyrosinase non-competitively by forming an enzyme-inhibitor complex. The inhibition constant Ki (0.09 µM) for compound 5 was calculated from Dixon plots. Computational results also displayed that all compounds possessed good binding profile against tyrosinase and interacted with core residues of target protein.

Keywords

• bi-heterocycles
• 1-phenyl-piperazine
• sulfonamides
• tyrosinase
• chemical kinetics
• computational study