Anti-cancer and Immunomodulatory Evaluation of New Nicotinamide Derivatives As Potential VEGFR-2 Inhibitors and Apoptosis Inducers: and Studies

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2022 Aug 18

PMID 35980113

Authors

Reda G Yousef

Alaa Elwan

Ibraheem M M Gobaara

Ahmed B M Mehany

Wagdy M Eldehna

Souad A El-Metwally

Bshra A Alsfouk

Eslam B Elkaeed

Ahmed M Metwaly

Ibrahim H Eissa

Affiliations

Soon will be listed here.

Abstract

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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