Synthesis, cytotoxicity of Carnosine peptide analogues on mitochondria obtained from cancerous rats’ liver

Authors

• Mohammadreza Gholibeikian,a* Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, I.R. Iran.
• AmirrezaArvaneh b Department of Organic Chemistry, Faculty of Chemistry, University of Science and Technology, Tehran, I.R. Iran.

Abstract

In this study, HCC (Hepatocellular carcinoma) was induced by diethylnitrosamine (DEN), as an initiator, and 2-acetylaminofluorene (2-AAF), as a promoter. Mitochondria from cancerous rats liver for evaluation of the cytotoxic effect of dipeptide Carnosineanalogues was isolated and cellular parameters related to apoptosis signaling were then determined. Our results showed that high toxicity synthesized linear and cyclic Carnosine analogues with concentration 10  in MTT assay, a raise in mitochondrial reactive oxygen species (ROS) level, swelling in mitochondria, ATP generation, mitochondrial membrane potential ( ψm) collapse, release of cytochrome c and caspase-3 activation after exposure of mitochondria isolated from the Hepatocellular carcinoma (HCC group). Based on the overall results, cyclic Carnosine analogues rather than linear Carnosine analogues would be encouraging to develop new anticancer agents and may be considered as a promising complementary therapeutic agents for the treatment of HCC. The synthesized Carnosine analogues were characterized by using different methods such as, LC-MS, FT-IR.