Synthesis, predictions of drug-likeness, and pharmacokinetic properties of some chiral thioureas as potent enzyme inhibition agents

Abstract

A series of chiral thioureas (1 - 17) were synthesized from and tested for their anticholinesterase, tyrosinase, and urease enzyme inhibitor activities. Various phenylisothiocyanates were added to solution of ˪-cysteine in methanol: water (1: 1 v / v) at room temperature and stirred for 24 h. The precipitated solid was recrystallized from n-butanol. Pure compounds were characterized by NMR (1H and 13C), FTIR, and CHNS. Tertiary amine containing N-(4-(diethylamino)phenyl)-N’-(2-mercapto-carboxyethanyl)thiourea 17, N-(4-(dimethylamino)phenyl)-N’-(2-mercapto-carboxyethanyl)thiourea 16 and trimethoxy containing N-(3,4,5-trimethoxyphenyl)N’-(2-mercapto-carboxyethanyl)thiourea 14 were more active than galantamine against AChE and BChE enzymes. In tyrosinase enzyme inhibition activity, compound 14, 10, 12, 6, 13, and 11 exhibited higher tyrosinase inhibitory activity showing IC50 values of 1.1 ± 0.1, 1.5 ± 0.3, 1.6 ± 0.6, 1.9 ± 0.5, 2.2 ± 0.9 and 2.9 ± 0.2 mM, respectively. In urease enzyme inhibition activity assay, 17 showed higher activity. This work demonstrates the pharmacological significance of chiral thiourea derivatives synthesized from ˪-cysteine and shows their potential. There is a need to perform more in vitro and in vivo biological activities followed by clinical trials to bring such thiourea to the market.