Background: Due to the close relationship of diabetes with hypertension reported in various research, a set of pyridine derivatives with US FDA-approved drug cores were designed and integrated by artificial intelligence. Methods: Novel pyridines were designed and synthesized. Compounds MNS-1-MNS-4 were evaluated for their structure and were screened for their in vitro antidiabetic (α-amylase) activity and anticancer (HepG2) activity by methyl thiazolyl tetrazolium assay. Comparative 3D quantitative structure-activity relationship analysis and pharmacophore generation were carried out. Results: The study revealed MNS-1 and MNS-4 as good alternatives to acarbose as antidiabetic agents, and MNS-2 as a more viable, better alternative to doxorubicin in the methyl thiazolyl tetrazolium assay. Conclusion: This combination of studies identifies new and more active analogs of existing FDA-approved drugs for the treatment of diabetes.
Keywords: CoMFA; HepG2; antidiabetic; molecular docking; one-pot relay synthesis.