ASIAN JOURNAL OF CHEMISTRY ASIAN JOURNAL OF CHEMISTRY https://doi.org/10.14233/ajchem.2017.20356 INTRODUCTION Apoptosis is referred as programmed cell death [1]. It plays a crucial role in normal development and tissue homeostasis by facilitating the removal of unwanted, damaged or infected cells [1,2]. Impairment of the apoptotic signal promotes aberrant cell proliferation, agglomeration of genetic defects, ultimately resulting in tumorigenesis [3]. Therefore, induction of apoptosis in cancer cells is a target for developing potent antineoplastic drug in cancer treatment. It is an energy dependent process in which the characteristic morphological changes occur, it includes plasma membrane blebbing, exposure of phosphatidylserine at the external surface of the cell membrane, cell shrinkage, chromatin condensation and DNA fragmentation [3,4]. At the molecular level, apoptosis is tightly regulated by the activation of the aspartate-specific cysteine protease (caspase) 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 PREETHI SALIGRAMA DEVEGOWDA 1 , KYATHEGOWDANADODDI SRINIVAS BALAJI 2 , DODDAKUNCHE SHIVARAMU PRASANNA 3 , TORESHETTAHALLY RAMESH SWAROOP 4 , SHANKAR JAYARAMA 2 , LOKESH SIDDALINGAIAH 1,* and KANCHUGARAKOPPAL SUBBEGOWDA RANGAPPA 5,* 1 Department of Studies in Biotechnology, University of Mysore, Manasagangotri, Mysore-570 006, India 2 Department of Biotechnology, Teresian College, Siddarthanagar, Mysore-570 011, India 3 Department of Nanotechnology, Visvesvaraya Technological University, Center for Postgraduate Studies, Bengaluru Region, Muddenahalli, Chikkaballapur District-562 101, India 4 Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore-570 006, India 5 Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore-570 006, India *Corresponding authors: E-mail: boramma@rediffmail.com; rangappaks@yahoo.com Received: 18 October 2016; Accepted: 27 December 2016; Published online: 31 January 2017; AJC-18269 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 13 C 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. Keywords: Quinazoline, Ehrlich ascites carcinoma cells, Apoptosis. Asian Journal of Chemistry; Vol. 29, No. 4 (2017), 896-904 cascade. Activation of caspase cascade can be initiated through activation of the apoptotic pathway [5]. The distinguished extrin- sic and intrinsic apoptotic pathway is based on the involvement of adaptor molecules and initiator caspases. These two pathways are interlinked and the molecules in one pathway influence the other pathway [6]. The mitochondrial pathway is regulated by activating pro-apoptotoic proteins Bax and inhibiting the anti- apoptotic proteins Bcl2 of the Bcl-2 family [7-9]. Cellular stress induces pro-apoptotic protein Bax to migrate to the surface of the mitochondria, where it procreate pores in the mitochondrial membrane and permit the release of cytochrome C into cytoplasm. Once cytochrome C is released, it activates intiator caspases-9 and results in the cleavage of effector caspase -3, -6 and -7 [7,8,10]. The active caspase-3 and -7 specifically cleaves poly (ADP-ribose) polymerase (PARP) that will lead to the nucleosomal DNA frag- mentation [11,12]. Cleavage of a definite number of key proteins is very important for the development of apoptotic events.