Design and Synthesis of Quinazoline Bearing Thiazolotriazole Scaffolds as Potent EGFR Inhibitor for Anti-Breast Cancer Activity

A number of fused heterocyclic hybrids with central rings of thiazolotriazoles are synthesized and characterized by 1H NMR, 13C NMR and EI-MS techniques. The synthesized compounds showed variable degrees of efficacy in their in vitro cytotoxic activity against MCF-7, MDA-MB-231 and MCF-10A cell lines. Remarkably some analogues exhibited greater activity than the reference drugs, erlotinib. The most effective compounds, 6i, 6h and 6j, displayed significant EGFR tyrosine kinase inhibition and significant cytotoxicity, in accordance with the molecular docking investigations that revealed favourable binding contacts and energies inside the EGFR active region.