Design, characterization, and DFT exploration of new quinazoline-N-substituted analogs: Anti-cancer activity and molecular docking insights

In this study, we report the synthesis of a new series of quinazoline-N-4-fluorophenyl derivatives 4a-d and their antitumor activity against human cancer cells. The derivatives were confirmed by NMR (¹H & ¹³C) and LC–MS. Their cytotoxicity was assessed using the MTT assay on WI38, HCT116, and HepG2 cell lines. Compound 4b showed significant cytotoxicity with IC₅₀ values of 7.34 ± 0.7 µM and 4.36 ± 0.3 µM against HCT116 and HepG2 cells, respectively, while compound 4a exhibited moderate activity against WI38 cells (IC₅₀ = 31.86 ± 2.4 µM). Molecular docking studies indicated that all four compounds have good binding affinity toward CAIX (−37.40 kcal/mol).