Synthesis of quinazoline derivatives and their in vitro inhibition activity against MDA-MB-231 cells and A549 cells

Abstract

A series of novel 4-aniline quinazoline derivatives (Y1-Y26) were synthesised from 2-amino-6-nitrobenzoic acid based on the quinazoline parent nucleus via trifluoroacetylation, ring-closing and chlorination; The CCK-8 method was used to assess the in vitro inhibitory activities of the resulting compounds against two distinct cell lines: breast cancer cells (MDA-MB-231) and non-small cell lung cancer (A549). The results demonstrated that most of the compounds exhibited in vitro proliferation inhibitory activity against both MDA-MB-231 and A549 cells. Among these, compound Y22 exhibited the strongest inhibitory effect on MDA-MB-231 cells (IC₅₀ = 4.53 μM); As the concentration of Y22 increased, the inhibition of cell proliferation was enhanced, and the cells gradually shrank and underwent morphological changes consistent with apoptosis; Transwell assay demonstrated that the compound Y22 exhibited a substantial inhibitory effect on cell migration; Flow cytometry revealed a substantial augmentation in apoptosis with elevated compound concentrations; Western blot analysis indicated that Y22 may exert in vitro antitumour activity by decreasing the expression of the anti-apoptotic protein Bcl-2 while increasing the expression of the pro-apoptotic protein Bax. The findings of these studies suggest that Y22 can potentially plays a significant role in the design and synthesis of antitumour drugs.