Synthesis, characterization, and in silico studies of new benzohydrazide derivatives targeting EGFR kinase

Tetrazole–imidazole hybrid derivatives as potential EGFR tyrosine kinase inhibitors: design, synthesis and in silico evaluation with preliminary antiproliferative assessment

Design, Synthesis, and In Silico Evaluation of Novel Benzimidazole-Based Urea Derivatives Targeting VEGFR-2

The newly synthesized benzimidazole-urea derivatives exhibit potential VEGFR-2 inhibitory activity, favourable binding properties and drug likeliness and could be more extensively tested in biological systems as anti-angiogenic and anticancer drugs.

Design and Synthesis of 2,4-Thiazolidinedione-Based Derivatives as Potent EGFR-Targeting Anticancer Agents

Structural–activity relationship analysis revealed the importance of the TZD core, electron-rich aromatic moieties, and balanced lipophilicity for enhanced anticancer activity, identifying TZD hybrids as promising EGFR-targeted anticancer leads.

In Silico Exploration of Novel EGFR T790M and C797S Resistance with Mutant-Selective Allosteric Inhibitors Using a Hybrid Computational Approach

A number of lead candidates with strong EGFR inhibitory potential, promising pharmacokinetic profiles, and mutant selectivity were successfully identified by the integrated computational approach.

Synthesis, characterization, molecular docking and pharmacokinetics of new pyrimidine carboxylate derivatives as potent VEGFR inhibitors

This study shows that the synthesized pyrimidine carboxylates bind effectively with VEGFR active site, demonstrate favourable pharmacokinetic properties and high oral bioavailability.

Integrated In Silico and In Vitro Discovery of a VEGFR-2-Targeted Anticancer Benzanilide Lead

The development of selective vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors remains a promising strategy for anticancer therapy targeting tumor angiogenesis. In the study at hand, a novel benzanilide-based derivative, ACEB-Cl, was rationally designed by assimilating fundamental pharmacophoric characteristics essential for VEGFR-2 inhibition. ACEB-Cl was evaluated using a comprehensive approach that combined computational modeling, synthesis, and in vitro biological assessment. Density functional theory (DFT) calculations revealed a favorable electronic profile, with distinct nucleophilic and electrophilic regions that could support potential interactions within the VEGFR-2 binding pocket. Docking and molecular dynamics (MD) simulations suggested stable binding of ACEB-Cl within the ATP-binding pocket, supported by strong hydrophobic interactions and favorable binding free energy (ΔG = −63.21 kcal/mol). Following synthesis, ACEB-Cl confirmed potent anti-VEGFR-2 activity in an ELISA-based assay (IC50 = 0.086 0.002 M), showing higher potency than sorafenib. Western blot analysis further confirmed significant downregulation of phosphorylated VEGFR-2 in MDA-MB-231 cells. In vitro cytotoxicity studies revealed selective anticancer activity, with reduced toxicity toward normal Vero cells and favorable selectivity indices. Mechanistically, ACEB-Cl triggered G0/G1 phase arrest and significantly increased apoptotic cell death, highlighting its ability to suppress cancer cell proliferation. Additionally, ADMET and toxicity estimations indicated a balanced pharmacokinetic and safety profile, with improved solubility, acceptable absorption, and reduced toxicity risks compared to sorafenib. Overall, this integrated study pinpointed ACEB-Cl as a promising VEGFR-2targeted anticancer lead compound with strong inhibitory potency, and a clearly defined mechanism of action, supporting its progression for further improvement.