Discovery of enaminone-linked benzofuran derivatives as dual VEGFR-2/hCA IX inhibitors exhibiting hypoxia-mediated chemosensitization
Wagdy M. Eldehna, Zainab M. Elsayed, Mohamed R. Elnagar, Andrea Ammara, Mahmoud S. Elkotamy, Rehan Monir, Alessio Nocentini, Mohammad M. Al‐Sanea, Claudiu T. Supuran, Haytham O. Tawfik, Hatem A. Abdel‐Aziz, Ahmed T. Negmeldin
Abstract
ADMET predictions confirmed its drug-like profile, whereas molecular docking revealed advantageous interaction inside the ATP-binding site of VEGFR-2 and the zinc pocket of hCA IX. All things considered, compound 4a shows great promise as a dual-target inhibitor and potential chemosensitizer for the treatment of malignancies caused by hypoxia.
Topics & Concepts
ChemistryBenzofuranEnzymeCombinatorial chemistryChemosensitizerSelectivityCarbonic anhydraseDoxorubicinStereochemistryDocking (animal)Active siteBiochemistryPharmacologyApoptosisDrugCancer researchStructure–activity relationshipChalconeTumor cellsEnzyme inhibitorDrug discoveryDual roleEnzyme function and inhibitionCancer, Hypoxia, and MetabolismHistone Deacetylase Inhibitors Research