Synthesis, Kinetics, Binding Conformations and Structure-activity Relationship of Potent Tyrosinase Inhibitors: Aralkylated 2-aminothiazole-ethyltriazole Hybrids.

Butt, Abdul Rehman Sadiq; Abbasi, Muhammad Athar; Aziz-ur-Rehman; Siddiqui, Sabahat Zahra; Raza, Hussain; Hassan, Mubashir; Shah, Syed Adnan Ali; Sung-Yum Seo

Considering the diversified pharmacological importance of thiazole and triazole heterocyclic moieties, a unique series of S-aralkylated bi-heterocyclic hybrids, 7a-l, was synthesized in a convergent manner. The structures of newly synthesized compounds were characterized by ¹H-NMR, 13C-NMR, IR, and EI-MS spectral studies. The structure-activity relationship of these compounds was envisaged by analyzing their inhibitory effects against tyrosinase, whereby all these molecules exhibited potent inhibitory potentials relative to the standard used. The Kinetics mechanism was ascertained by Lineweaver-Burk plots, which revealed that 7g inhibited tyrosinase non-competitively by forming an enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.0057µM. These bi-heterocyclic molecules also disclosed good binding energy values (kcal/mol) when assessed computationally. So, these molecules can be considered promising medicinal scaffolds for the treatment of skin disorders.

PHENOL oxidase; STRUCTURE-activity relationships; BINDING energy; CHEMICAL synthesis; MOIETIES (Chemistry); TRIAZOLES; ENZYME kinetics

Iranian Journal of Pharmaceutical Research, 2021, Vol 20, Issue 2, p206

Academic Journal

10.22037/ijpr.2020.15521.13145