Synthesis, Biological Evaluation, and Docking Studies of New 2‐Furylbenzimidazoles as Anti‐Angiogenic Agents: Part II

Abstract

The 2-(5-methyl-2-furyl)-1H-benzimidazole moiety has shown promising activity against vascular endothelial growth factor (VEGF)-induced angiogenesis. In part I of this study, we have synthesized new analogs and tested their anti-angiogenic potentials. Here, we continue our previous study with different new analogs. Some compounds show promising cytotoxic activity against the human breast cancer cell line MCF-7, with IC50 in the range of 7.80-13.90 µg/mL, and exhibited remarkable in vitro inhibition against VEGF in the MCF-7 cancer cell line, with 95-98% of inhibition in comparison to tamoxifen as reference (IC50: 8.00 µg/mL, % of inhibition = 98%). Additionally, a molecular docking study was carried out to gain insight into plausible binding modes and to understand the structure-activity relationships of the synthesized compounds.

Targeting Receptor Tyrosine Kinase VEGFR-2 in Hepatocellular Cancer: Rational Design, Synthesis and Biological Evaluation of 1,2-Disubstituted Benzimidazoles

“…The designed molecules successfully showed promising VEGFR-2 inhibitory activity in comparison to their parent compound NP184 (VII). In silico, molecular docking simulations showed that the 2-furylbenzimidazole scaffold occupies the allosteric hydrophobic back pocket, while the chain in position one of the benzimidazole moiety extends to the gate area stabilizing the molecule through two hydrogen bonds with the key amino acids Glu885 and Asp1046, achieving VEGFR-2 inhibition in a type III inhibitor-like binding mode [17,47].…”

Synthesis,in vitroandin vivoantitumor and antiviral activity of novel 1-substituted benzimidazole derivatives

“…It was evident that 1-(4-bromobenzyl) benzimidazole derivative III was the most potent androgen receptor antagonist for prostate cancer 19 . This is in addition to our very recent published work in synthesis of novel series of cytotoxic benzimidazole derivatives [20][21][22] . Moreover, many antiviral substituted benzimidazoles at position 1 were either clinically applied or evaluated using a wide range of virus strains 23,24 .…”

Triterpenes from Poria cocos are revealed as potential retinoid X receptor selective agonists based on cell and in silico evidence

“…Despite the limitations of computational approaches, the molecular docking study was carried out to provide insight into the binding interactions for the best fit conformations in the binding site of the RXR protein and identify compounds with potential ability to become RXR agonists (Temirak et al, ). Before docking, we employed a validation of the molecular docking protocol using the extracted native ligand K09 from the binding site of RXR and re‐docked it into the protein (Tian, Wang, Li, Xu, & Hou, ).…”