Synthesis, and In Vitro and In Silico alpha-Glucosidase Inhibitory Studies of 5-Chloro-2-Aryl Benzo[d]thiazoles

Twenty-five derivatives of 5-chloro-2-aryl benzo[d]thiazole (1-25) were synthesized and evaluated for their alpha-glucosidase (S. cerevisiae EC 3.2.1.20) inhibitory activity in vitro. Among them eight compounds showed potent activity with IC50 values between 22.1 +/- 0.9 and 136.2 +/- 5.7 mu M, when compared with standard acarbose (IC50 = 840 +/- 1.73 mu M). The most potent compounds 4, 9, and 10 showed IC50 values in the range of 22.1 +/- 0.9 to 25.6 +/- 1.5 mu M. Compounds 2, 5, 11, and 19 showed IC50 values within the range of 40.2 +/- 0.5 to 60.9 +/- 2.0 mu M. Compounds 1 and 3 were also found to be good inhibitors with IC50 values 136.2 +/- 5.7 and 104.8 +/- 9.9 lM, respectively. Their activities were compared with alpha-glucosidase inhibitor drug acarbose (standard) (IC50 = 840 +/- 1.73 mu M). The remaining compounds were inactive. Structure-activity relationships (SAR) have also been established. Kinetics studies indicated compounds 2, 3, 10, 19, and 25 to be non-competitive, while 1, 5, 9, and 11 as competitive inhibitors of alpha-glucosidase enzyme. All the active compounds (1-5, 9-11, and 19) were also found to be non-cytotoxic, in comparison to the standard drug i.e., doxorubicin (IC50 = 0.80 +/- 0.12 mu M) in MTT assay. Furthermore, molecular interactions of active compounds with the enzyme binding sites were predicted through molecular modeling studies. (C) 2018 Elsevier Inc. All rights reserved.