Synthesis of Promising Biguanide Derivatives Bearing Urea/Thiourea as Type II Antidiabetic Agents

Novel biguanide hydrochloride salts were synthesized through the reaction of N ‐substituted‐semi(thiosemi)carbazides with cyanoguanidine in an acidic medium. Antidiabetic properties of the synthesized biguanides were evaluated for their antidiabetic properties. All biguanide compounds showed promising effects, which revealed a significant decrease in the elevated glucose in comparison with metformin on oral treatment of hyperglycemic rats with the synthesized biguanide derivatives. The monosubstituted thiourea showed an improvement by about 1.48‐fold of metformin. The effect of the synthesized biguanides on liver function enzyme activities, lipid profiles, and renal functions was investigated and discussed as compared with normal control rats; some urea derivatives showed improvement results that were nearly equal to those of metformin. Regarding lipid profile, the N ‐phenylurea moiety showed improved results higher than metformin. Regarding the effect on kidney function markers, some urea derivatives showed results that were higher than those of metformin. Also, antioxidant biomarkers and inflammatory markers were detected in diabetic rats and discussed; the results of all tested derivatives were equal to twofold of the results of metformin. Moreover, the histopathological examination of hepatic, kidney, and pancreatic tissues reveals that all of the tested compounds showed significant, promising activity.