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Anti-cancer and immunomodulatory evaluation of new nicotinamide derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: and studies. | LitMetric
New nicotinamide derivatives , , , and were designed and synthesised based on the essential features of the VEGFR-2 inhibitors. Compound revealed the highest anti-proliferative activities with IC values of 15.4 and 9.8 µM against HCT-116 and HepG2, respectively compared to sorafenib (IC = 9.30 and 7.40 µM). Compound owned promising cytotoxic activities with IC values of 15.7 and 15.5 µM against the same cell lines, respectively. Subsequently, the VEGFR-2 inhibitory activities were assessed for the titled compounds to exhibit VEGFR-2 inhibition with sub-micromolar IC values. Moreover, compound induced the cell cycle cessation at the cycle at %G2-M and G0-G1phases, and induced apoptosis in the HCT-116. Compounds and reduced the levels of TNF- by 81.6 and 84.5% as well as IL-6 by 88.4 and 60.9%, respectively, compared to dexamethasone (82.4 and 93.1%). docking, molecular dynamics simulations, ADMET, and toxicity studies were carried out.
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