Exploration of the anticancer efficacy of a novel 1,3-thiazole analog in an ehrlich ascites carcinoma model: and insights into hepatorenal protective potentials the modulation of apoptosis, oxidative stress and inflammation.

Thiazoles, as a class of compounds, offer a diverse array of analogs that are pivotal in the rational design of anticancer agents. Recently, we reported a novel 1,3-thiazole analog, 2-(1-(2-(4-(4-bromophenyl)thiazol-2-yl)hydrazinylidene)ethyl)phenol (BTHP), that exhibited potential cytotoxic activity toward breast cancer cells. In the present study, we extended our investigations to explore the anticancer potential of BTHP in Ehrlich Ascites Carcinoma (EAC)-administrated female Swiss albino mice. Our findings revealed that, compared with the control group, the expression levels of antioxidant enzymes significantly decreased in the EAC-induced model group, while the level of lipid peroxidation substantially increased. Furthermore, the administration of EAC impaired hepatorenal function, as indicated by a significant increase in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea levels and a decrease in total protein and albumin levels. EAC-induced renal and hepatic damage was accompanied by elevated expression of proinflammatory biomarkers (TGF-β, NFκB, and IL6 genes) and altered serum apoptotic signaling, including reduced p53, Bax, caspase-3, and cytochrome c levels, alongside increased Bcl-2 expression. Interestingly, administration of BTHP (5 mg per kg per day, 14 days) significantly mitigated the viable EAC cell count (38%) and enhanced lifespan (131.25%) compared to untreated EAC-bearing mice. Furthermore, compared with the EAC-induced model group, the BTHP-treated EAC-induced group exhibited significantly attenuated lipid peroxidation levels and enhanced antioxidant enzyme activity (superoxide dismutase, glutathione, and catalase). Moreover, BTHP improved hepatorenal function by restoring serum ALT, AST, urea, creatinine, albumin, and total protein levels. Remarkably, BTHP reversed the apoptotic dysregulation observed in the EAC model, significantly elevating p53, Bax, caspase-3, and cytochrome c levels while suppressing Bcl-2 expression. Anti-inflammatory effects were further evidenced by diminished NFκB, TGF-β, and IL6 expression in liver and kidney tissues. Histological examinations confirmed BTHP's efficacy in attenuating EAC-induced renal and hepatic damage, preserving structural integrity. Finally, detailed molecular modeling investigations revealed that BTHP exhibits a pronounced binding affinity toward key protein targets associated with the observed anticancer activity. Overall, this study underscores the anticancer efficacy of BTHP through the regulation of antioxidant, proinflammatory, and apoptotic biomarkers, highlighting its protective effects on hepatorenal function and its therapeutic potential.