One-pot multicomponent synthesis of novel pyridine derivatives for antidiabetic and antiproliferative activities.
Nusrat ShafiqNabeel ShahzadFatima RidaZaheer AhmadHafiza Ayesha NazirUzma ArshadGul ZareenNaila AttiqShagufta ParveenMaryam RashidBasharat AliPublished in: Future medicinal chemistry (2023)
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 was 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.
Keyphrases
- blood pressure
- structure activity relationship
- artificial intelligence
- type diabetes
- cardiovascular disease
- machine learning
- big data
- high throughput
- molecular docking
- glycemic control
- deep learning
- drug administration
- drug delivery
- molecular dynamics
- gene expression
- genome wide
- single cell
- metabolic syndrome
- drug induced
- electronic health record
- case control