Synthesis and Computational Exploration of Morpholine Bearing Halogenated Sulfonamides as Potential Tyrosinase Inhibitors

Abstract

In the presented work, a novel series of three different 4‐((3,5‐dichloro‐2‐[(2/4‐halobenzyl)oxy]phenyl)sulfonyl)morpholines was synthesized and the structure of these compounds were corroborated by 1H‐NMR & 13C‐NMR studies. The in vitro results established all the three compounds as potent tyrosinase inhibitors relative to the standard. The Kinetics mechanism plots established that compound 8 inhibited the enzyme non‐competitively. The inhibition constants Ki calculated from Dixon plots for this compound was 0.0025µM. Additionally, computational techniques were used to explore electronic structures of synthesized compounds. Fully optimized geometries were further docked with tyrosinase enzyme for inhibition studies. Reasonably good binding/interaction energies and intermolecular interactions were obtained. Finally, drug likeness was also predicted using the rule of five (RO5) and Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. It is anticipated that current experimental and computational investigations will evoke the scientific interest of the research community for the above‐entitled compounds.

Design of potent tyrosinase inhibiting N-arylated-4-yl-benzamides bearing 2-aminothiazole-triazole bi-heterocycles: mechanistic insight through enzyme inhibition, kinetics and computational studies

“…A series of experiments were performed to determine the inhibition kinetics of 9c by following the already reported methods. 41,42 The inhibitor concentrations for 9c were 0.00, 0.004, 0.008, 0.016 and 0.032 μM. Substrate l -DOPA concentrations were between 0.125 and 2 mM in all kinetic studies.…”