Details

Autor(en) / Beteiligte

• Elkaeed, Eslam B
• Yousef, Reda G
• Khalifa, Mohamed M
• Ibrahim, Albaraa
• Mehany, Ahmed B. M
• Gobaara, Ibraheem M. M
• Alsfouk, Bshra A
• Eldehna, Wagdy M
• Metwaly, Ahmed M
• Eissa, Ibrahim H
• El-Zahabi, Mohamed Ayman

Titel

Discovery of New VEGFR-2 Inhibitors: Design, Synthesis, Anti-Proliferative Evaluation, Docking, and MD Simulation Studies

Ist Teil von

• Molecules (Basel, Switzerland), 2022-09, Vol.27 (19), p.6203

Ort / Verlag

Basel: MDPI AG

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Electronic Journals Library - Freely accessible e-journals

Beschreibungen/Notizen

• Four new nicotinamide-based derivatives were designed as antiangiogenic VEGFR-2 inhibitors. The congeners were synthesized possessing the pharmacophoric essential features to bind correctly with the VEGFR-2 active pocket. All members were evaluated for their cytotoxic and VEGFR-2 inhibitory potentialities. Compound 6 was the most potent showingIC50 values of 9.3 ± 0.02 and 7.8 ± 0.025 µM against HCT-116 and HepG-2 cells, respectively, and IC50 of 60.83 nM regarding VEGFR-2 enzyme inhibition. Compound 6 arrested the growth of HCT-116 cells at the pre-G1 and G2-M phases. Further, it induced both early and late apoptosis. Additionally, compound 6 caused a significant decrease in TNF-α and IL6 by 66.42% and 57.34%, respectively. The considered compounds had similar docking performances to that of sorafenib against the VEGFR-2 (PDB ID: 2OH4). The correct binding of compound 6 with VEGFR-2 was validated using MD simulations, and MM-GPSA calculations.