Pro-Apoptotic Activity of Novel 4-Anilinoquinazoline Derivatives Mediated by Up-Regulation of Bax and Activation of Poly(ADP-ribose) Phosphatase in Ehrlich Ascites Carcinoma Cells

Abstract

Quinazolines are very important class of heterocyclic compounds with antitumor properties. In search of novel anti-tumour agents, a series of 4-anilinoquinazolines were synthesized and characterized using proton and ¹³C NMR, Fourier transform infrared and mass spectroscopic techniques. These compounds were evaluated for their cytotoxic effect on ehrlich ascites carcinoma cells using MTT assay. Among the tested compounds, compound N-(3-((6,7-dimethoxyquinazoline-4-yl)amino)phenyl)-4-nitrobenzene sulfonamide exhibited more potent activity with an IC₅₀ value of 10.29 ± 1.14 μM against ehrlich ascites carcinoma cell line. in vivo studies using compound N-(3-((6,7-dimethoxyquinazoline-4-yl)amino)phenyl)-4-nitrobenzene sulfonamide (4G) showed that there was reduction in the mice body weight, ascites volume and decrease in cell number. Mice treated with compound 4G showed higher survivability compared with that of control mice. The cells treated with compound 4G also exhibited typical morphological changes of apoptotic damages. Further, compound 4G induced tumour cell death by activating pro-apoptotic protein Bax which activates caspase-3 which in turn cleaves poly (ADP- ribose) polymerase and causes DNA fragmentation. Thus, our results strongly conclude that our compound 4G acts as a antincancer agent by inducing apoptosis in ehrlish ascites carcinoma cells.