Coumarin-triazine hybrid pharmacophores as new EGFR inhibitors against cancer cell lines: Synthesis, computational studies, and in vitro cytotoxic evaluation

Abstract

A new line of triazine-benzopyran hybrid compounds, 1,3,5-triazin-2-yl) oxy)-4-methyl-2H- chromen-2- ones, has been developed, synthesized, and physiologically explored as epidermal growth factor receptor (EGFR) inhibitors for cancer treatment. The work used pharmacophore hybridization to increase receptor affinity and anticancer properties by combining the physiologically active coumarin nucleus with a 1,3,5-triazine ring. Derivatives 4a-4d had good hydrogen bond and hydrophobic contacts with the key amino acid residues Met793, Lys745, Thr790, and Leu718 in the EGFR Adenosine triphosphate-binding pocket. The synthesis of new derivatives was carried out using cyanuric chloride and 7-hydroxy-4- methyl-coumarin as starting materials. The MTT assay was used to test the synthesized compounds' cytotoxicity against BT-549, HT-29, HeLa, and MCF-7 cells. The structure-activity relationship suggested that morpholine residue on the triazine ring considerably increased anticancer activity, but bulky aromatic replacements lowered it. In conclusion, triazine- benzopyran hybrids may be lead compounds for EGFR-targeted anticancer medicines and warrant further mechanistic and pharmacological research.. KEYWORDS :Coumarin, Epidermal growth factor receptor inhibitors, Hybridization, MTT assay, Pharmacophore, Triazine.