Synthesis and hyperglycemic, biochemical and histopathological evaluation of novel sulfonylbiguanide and sulfonylurea derivatives as potent anti-diabetic agents.

New sulfonylbiguanide hydrochloride salts and sulfonylurea derivatives containing two sulfonyl groups were synthesized through the reaction of arylsulfonohydrazides with cyanoguanidine and p-tolylsulfonylisocyanate, respectively. Oral treatment of hyperglycemic rats with the synthesized sulfonylbiguanide derivatives 2 and sulfonylurea derivatives 3 revealed that sulfonylurea derivatives 3a and 3c possessed significant decrease of the elevated glucose in compression with the anti-diabetic standard drugs. Effects of the synthesized sulfonylurea derivatives 3a and 3c on the diabetic properties towards α-amylase, liver function enzyme levels (AST, ALT, ALP, TB and γ-GT), kidney functions (urea and creatinine), lipids profiles (TG, TL, TC and HDL-C) were studied. Also, the effect of sulfonylurea derivatives 3a and 3c as antioxidants (reduced glutathione and lipid peroxide) was evaluated. Histopathological examination of hepatic and pancreatic tissues was investigated. The obtained results suggested that the most potent sulfonylurea derivatives 3a and 3c might be possible used as novel diabetic inhibitor agents.