Design, synthesis, and anticancer evaluation of novel pyrazole–thiophene hybrid derivatives as multitarget inhibitors of wild EGFR, mutant (T790M) EGFR, and VEGFR-2
Mohammed N. Sallam, Ahmed A. Al‐Karmalawy, Eslam M. Abbass, Samia S. Hawas, Abeer M. El‐Naggar, Mohd Ali Hassan
Abstract
55.31% in control), increased the apoptotic population to 26.32%, and caused minimal necrosis (4.2%). Molecular docking supported these findings, revealing strong binding affinities and favorable interactions of 2, 14, and 8 with EGFR (wild-type and T790M mutant) and VEGFR-2, respectively. Taken together, these results highlight 2, 8, and 14 as promising pyrazole-thiophene multitargeted anticancer leads, offering potential for further optimization to overcome kinase-driven resistance in cancer therapy.
Topics & Concepts
ChemistryMutantCytotoxicityT790MDocking (animal)ApoptosisCell cultureEGFR inhibitorsPopulationEnzymeBiochemistryCancer cell linesCancer cellCellBinding affinitiesSelectivityBiological activityPharmacologyHEK 293 cellsStructure–activity relationshipCancer researchMutationCancerRational designComputational biologyActive siteWild typeLung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchSynthesis and biological activity