Design, Synthesis, and Biological Evaluation of Aminophenol-Quinazoline-Based Derivatives as Antiproliferative Agents...

Quinazoline-based scaffolds are well recognized for their therapeutic potential, particularly in the development of anticancer agents targeting tyrosine kinase-mediated signaling pathways. In the present study, a series of novel quinazoline derivatives bearing cyclopropane-1,1-dicarboxamide moieties were designed, synthesized, and evaluated for their anticancer activity against human colorectal cancer (CRC) cell lines. The synthesized compounds were structurally characterized using 1H and 13C NMR spectroscopy and high-resolution mass spectrometry. Their in vitro antiproliferative activity was assessed against HT-29 and COLO-205 cell lines using the MTT assay, with cabozantinib serving as the reference standard. Several compounds demonstrated promising cytotoxic activity, with compound SQ14 exhibiting the most potent inhibitory effect, comparable to the standard drug. Molecular docking and molecular dynamics simulations were performed to elucidate binding interactions and stability within the active site of the target protein, revealing favorable binding orientations and key intermolecular interactions. Furthermore, in silico ADMET analysis supported the drug-like nature and acceptable pharmacokinetic profiles of the lead compounds. Overall, the integrated experimental and computational findings suggest that the newly synthesized quinazoline derivatives, particularly SQ14, represent promising candidates for further development as potential anticancer agents against CRC.