SYNTHESIS AND ANTICANCER EVALUATION OF NOVEL HETEROCYCLICS DERIVED FROM IMIDAZOLE AND QUINOLINE SCAFFOLDS

Abstract

Cancer is one of the leading diseases responsible for high mortality rates worldwide. It develops when normal cells begin to grow out of control in particular part of the body. There are different types of cancer, all types of cancer cells continue to grow, divide and re-divide forming new abnormal cells. Persistent failure to ensure complete remission and eradication of cancer stimulated the search for new anticancer agents. The imidazole and quinoline based heterocyclics were rationally designed and synthesized as anticancer agents. The compounds were screened against various cancer cell lines for the assessment of their cytotoxic potential. The compounds were found to be non-cytotoxic to Human Peripheral Blood Mononuclear Cells (hPBMC).The mechanistic studies were carried out on potent compounds via cell reactive oxygen species (ROS) assay and JC-1 based mitochondrial permeability assay. The compounds were found to increase ROS levels and disrupt the mitochondrial membrane integrity. Further the quinoline based compounds were evaluated for EGFR inhibitory potential and topoisomerase inhibition. The RT- PCR, real time PCR, cell cycle analysis and DNA content analysis provided a light to their mechanistic interventions at molecular levels. The synthesized compounds offer the generation of library of compounds for structure activity relationship studies, further tracing their molecular mechanism(s) and biophysical studies in addition to their development at preclinical level. newline