Synthesis, in silico, in vitro and in vivo studies of novel natural-based arylidenes curcumin as potential glycohydrolase digestive enzymes inhibitors

Abstract

Diabetes is one of the most common metabolic diseases in humans and the use of herbal medicines is of great clinical importance to inhibit carbohydrate-hydrolyzing enzymes and reduce blood glucose levels in diabetic patients. Inhibition of glycosidase activity is an effective way to treat and prevent diabetes. Therefore, in this study, curcumin-based benzaldehyde derivatives were synthesized and used as influential agents in the treatment of diabetes with inhibitory properties against two carbohydrate-hydrolyzing enzymes α-glucosidase (α-Glu) and α-amylase (α-Amy) as significant therapeutic targets for reducing postprandial hyperglycemia. Overall, the findings showed that due to the specific inhibitory activity against α-Glu in comparison with α-Amy, as well as more stability and antioxidant activity than curcumin, C5 and C8 derivatives are potentially important anti-diabetic drugs, not only to decrease glycemic index but also to limit the activity of the main production pathways of reactive oxygen species (ROS) in diabetic patients.

Communicated by Ramaswamy H. Sarma

Keywords:

• Antioxidant
• curcumin
• α-amylase
• α-glucosidase
• antidiabetic

Acknowledgments

The financial supports from the Research Council of Kermanshah University of Medical Sciences are gratefully acknowledged (Grant No. 990347/990348). This work was performed in partial fulfillment of the requirements for Pharm. D. of Mohammad Mahdi H. Yazdi, in Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Author’s contributions

R.K. and H.A. designed the study and with M.E. were involved in statistical analysis and data management. M.E., K.S.J and M.M.H.Y. performed the experiments under supervision of R.K. and H.A. as well. R.K., M.E. and F.G. as well as R.H.S. drafted this article. All authors were involved in critical revision of the manuscript and final approval of the published version.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

Additional information

Funding

The financial supports from the Research Council of Kermanshah University of Medical Sciences are gratefully acknowledged (Grant No. 990347/990348).