Synthesis of sulfonylthioureas as anti-diabetic drugs

Abstract

This dissertation discussed the synthesis, cytotoxicity and alpha-glucosidase inhibition of sulfonamides and novel sulfonylthiourea compounds. Three series of novel sulfonylthiourea [benzamido-benzenesulfonylthiourea (28a-28d), pyrrolidino-benzenesulfonylthiourea (33a-33c) and acetamido-benzenesulfonylthiourea (26a-26k) were successfully synthesized in moderate yields to excellent yields. Four novel benzamido-benzenesulfonylthiourea 28a, 28b, 28c and 28d were obtained from reactions of benzamido-benzenesulfonamide with four isothiocyanates. Three novel pyrrolidino benzenesulfonylthiourea 33a, 33b and 33c were obtained from the reactions of pyrrolidino benzenesulfonamide with three isothiocyanates. Five acetamido-benzenesulfonylthioureas 26a-26k were obtained from reactions of acetamido-benzenesulfonamide with four different isothiocyanates. All synthesized compounds were successfully characterized by 1H NMR, 13C NMR, DEPT 135, mass spectrometry and melting points. Benzenesulfonamides 25a-25e, 32, and 27, benzenesulfonylthioureas 28a-28d, 33c, 26a-26e were subjected to in-vitro cyctotoxicity screening against Caco2 cells at concentration of 100 μM and were found to be non-toxic against Caco2 cells. These compounds were then subjected to in-vitro α-glucosidase inhibition study at concentrations of 10 μM, 50 μM, 100 μM and 200 μM. 4-(2-Morpholine-acetamido)-benzenesulfonamide 25-e showed the most promising α-glucosidase inhibition with 95% inhibition at concentration of 50 μM and 98 % inhibition at concentration of 100 μM. Compounds 28-c, 26-b, 26-c and 26-d showed significant improved α-glucosidase inhibition at 200 μM concentration with percent inhibition ranging between 50% and 81%. The study revealed that both sulfonamides and sulfonylthiourea can potentially be used as anti-diabetic agents.