Synthesis, Molecular Docking Analysis and In vitro Evaluation of Potential Anti-Diabetic Candidates with Harnessing the Effectiveness of Scoparia Dulcis Plant

Natural products have involved and persistent in playing an essential part for the search of novel entities in the treatment of various diseases since antiquity. Scoparia dulcis (S. dulcis), commonly known as a sugar lowering weed, is recognized for its insulin secretagogue properties. Current research explores the potential of a library of small molecules, derived from the active constituents of S. dulcis, designed to target receptors and exhibit insulin secretagogue effects similar to sulfonylurea drugs, which are well-known insulin secretory agents.

The designed novel molecules were analysed by molecular docking studies of selected protein 5yw7 (A pancreatic ATP-sensitive potassium channel, KATP) bound with an internal ligand glibenclamide. Compounds were synthesized in 3 different series as derivatives of benzoxazolinone, benzimidazolones, and benzimidazole thiones. The molecules showed better binding scores as compared to the active chemical constituents of S.dulcis were coded as 1b,1 g,1b,2c, 2 h,3b & 3 f. Furthermore, In silico toxicity and ADME profile were checked by SWISS ADME & Lazar toxicity software’s. The In vitro evaluation of the selected molecules was performed using rat insulin ELISA assay.

The calculated lipophilicity (iLogP) of synthesized compounds was found in the range of 0.76 to 1.88. The percentage insulin secretion of the test compounds were calculated using insulin ELISA assay results. Synthesized compound 1b (135.05 ± 6.19) and 2 h (131.06 ± 2.99) showed most potent effect at 100 µM dose. Statistically, the results of relative insulin secretion at 100 µM dose were significant with ***p < 0.001, **p < 0.01 and *p < 0.05.

The current investigation highlights the effectiveness of nitrogen containing alkaloids isolated from Plant S. dulcis and emphasize the potential of synthesized compound 1b an 2 h as insulin secretory agents which can be further considered for developing novel antidiabetic agents.