Synthesis and Evaluation of Antihyperglycemic Activity of 1, 4-Benzothiazepine-2-One Derivatives in Alloxan Induced Diabetic Rats
Department of Pharmacy, Laboratory of Medicinal and Pharmaceutical Chemistry, Shri Govindram Seksaria Institute of Technology and Science, Indore, Madhya Pradesh 452003, India
Meena Tiwari, Department of Pharmacy, Laboratory of Medicinal and Pharmaceutical Chemistry, Shri Govindram Seksaria Institute of Technology and Science, Indore, Madhya Pradesh 452003, India, E-mail: firstname.lastname@example.org
The present study reported the synthesis and antihyperglycemic activity of 1,4-benzothiazepines (1,4-benzothiazepine-2-one derivatives) in alloxan-induced diabetic rats. 1,4-benzothiazepines (3a-i) were synthesized via Friedel-Crafts acylation, reduction and microwave assisted S-alkylation reactions and characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, mass and elemental analysis. In silico absorption, distribution, metabolism, excretion and toxicity parameters of synthesized compounds 3a-i were found within their acceptable limits. In acute toxicity study, none of synthesized 1,4-benzothiazepines showed any toxicity risks such as tremor, convulsion, lacrimation, sedation, increased or decreased motor activity, etc., in Wistar rats. The antihyperglycemic activity showed that synthesized 1,4-benzothiazepines (3a-i) reduced the elevated blood glucose level significantly in Wistar rats. 3f, 3h and 3i with electronegative substitution at 7 position of benzothiazepine nucleus and at 2’ position of phenyl ring, showed better antihyperglycemic activity as compared to other 1,4-benzothiazepines having weak electronegative substituent at the same position. The antihyperglycemic activity of synthesized 1,4-benzothiazepines was comparable with antihyperglycemic activity of metformin and CGP37157. The present study may be helpful in development of novel antidiabetic agents.