A novel quinazoline-based compound, 4-(1-(2-amino-6,7-dimethoxyquinazolin-4-yl)-1,4- dihydropyridin-3-yl)methylbenzoic acid, was synthesized and characterized as a potential therapeutic agent targeting non-small-cell lung carcinoma (NSCLC) cells. The compound was prepared via a two-step synthetic process—alkylation followed by condensation—and its structure was confirmed through infrared (IR), nuclear magnetic resonance (NMR), mass spectrometry, and X-ray diffraction analyses. To evaluate its antiproliferative efficacy, a concentration-dependent cytotoxicity assay (MTT) was conducted using A549 human NSCLC cells. The compound exhibited strong cytotoxic potential with a calculated IC value of 19.88 μg/mL, alongside significant apoptotic induction confirmed by acridine orange/ethidium bromide (AO/EtBr) dual staining. Morphological assessment under microscopy revealed pronounced apoptotic features that increased in a time-dependent manner, with 57% and 66% apoptotic cells present at 24 and 48 hours, respectively. Molecular docking and induced fit docking studies against the KRAS^G12C protein (PDB: 7AIW) revealed high-affinity binding, stabilized by a network of hydrogen bonds and hydrophobic interactions involving critical active-site residues, reflected in a substantial MMGBSA binding energy (−39.25 kcal/mol) and an excellent docking score (−4.47). These findings demonstrate that the synthesized quinazoline derivative possesses promising anticancer activity mediated by apoptosis and strong interactions with oncogenic targets, highlighting its potential as a lead molecule for further mechanistic exploration and drug development against NSCLC.
Keywords: Synthesis Quinazoline derivative, A549 cell line, Cytotoxicity; Apoptosis, Insilico Studies
How to cite this article: Srinivasan M, Ismail Y.; Synthesis, Characterization, and Antiproliferative Evaluation of a Quinazoline-Based Compound Against A549 Non-Small-Cell Lung Carcinoma..Int J Drug Deliv Technol. 2026;16(1s): 303-310; DOI: 10.25258/ijddt.16. 303-310