Design, synthesis, and biological evaluation of coixol-based derivatives as potential antidiabetic agents

Natural products have great potential for structural modifications to achieve the desired biological ef-fect. In addition, these are considered safer, less expensive, and easily accessible compared to synthetic drugs. The natural compound coixol is a potent insulin secretagogue, obtained from the Plant parts of Scoparia dulcis and Coix lacryma jobi. In the present research work, we synthesized coixol-based deriva-tives that could potentially emerge as successful antidiabetic agents. Our previous work explains exclu-sive molecular docking studies based on the natural product coixol, which led to the current selection of twelve molecules comprising 2-benzoxazolinones, 2-benzimidazolinone, and benzimidazole-2-thiones with a good binding affinity toward ATP-sensitive potassium channel. All the synthesized molecules were screened for in vitro studies using a rat insulin ELISA assay. Wherein, Compounds 14a and 34 were identified as the most potent molecules with percentage insulin secretory concentrations of 162.43 and 227.16 mu U/mL respectively which was reportedly higher than the standard drug Glibenclamide. The in vivo antidiabetic effect was checked using the streptozotocin-induced Type-II diabetes rat model, which revealed that test compounds 14a and 34 significantly reduced plasma glucose and total cholesterol levels and a marked increase in plasma insulin response was observed in diabetic rats. The histopathological examination at the end of the protocol also showed an improvement in the pancreatic tissue of diseased animals treated with test compounds 14a and 34. Thus, this research work indicates that the synthe-sized derivatives of coixol, 14a and 34 have good potential to be used for treating and managing Type-II diabetes in the future.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

Natural products can be structurally modified to achieve desired biological effects, and they are considered safer, cheaper, and more easily accessible compared to synthetic drugs. This research synthesized coixol-based derivatives that may serve as effective antidiabetic agents. In vitro and in vivo experiments demonstrated that compound 14a and 34 have potential for treating Type-II diabetes.