Design and synthesis of new nicotinamides as immunomodulatory VEGFR-2 inhibitors and apoptosis inducers.

Background

Nicotinamide-based VEGFR-2 inhibitors have good contribution in drug discovery.Aim: Development of novel nicotinamides as VEGFR-2 inhibitors.

Methods

different in vitro and in silico assays were conducted to evaluate the VEGFR-2 inhibition and cytotoxicity.

Results

Compound 16c displayed strongest anti-VEGFR-2 potentiality and good anti-proliferative effects. Compound 16c enhanced apoptosis and caused cell cycle arrest in the Pre-G1 and S phases. Compound 16c boosted the level of the apoptotic caspase-3 and inhibited the level of TNF-α and IL-6 in tumor cells. Molecular docking and molecular dynamics (MD) simulations indicated the outstanding binding potential of compound 16c against VEGFR-2.

Conclusion

Compound 16c is a good candidate for the creation of a novel antiangiogenic lead anticancer medication.