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

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 l-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 ( 1 H and 13 C), 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 IC 50 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 l-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.