Investigation of anticancer activities of some visinal diaryl heterocyclic compounds

Cancer is defined as an uncontrolled cell proliferation, gaining pathological features by interacting with the environment. Although various treatment approaches have been developed, it continues to be an important problem affecting people's quality of life and survival. For this reason, many distinguished researchers have worked on developing new anticancer agents that are selective to cancer cells and have less side-effects aiming to increase the quality of life of the patients. According to the data of WHO, breast and liver cancers are among the most diagnosed cancer types. Based on the lead compound 5- methyl-4-(4-chlorophenyl)-3-(4-((2-methylbenzyl)oxy)phenyl)isoxazole (EB38) developed by our research group, 33 new compounds were synthesized within the scope of this thesis in order to develop new compounds effective against liver and breast cancer. The cytotoxic effects of these compounds against breast and liver cancer cell lines were determined to develop new compounds that more potently inhibit the proliferation of cancer cells as compared to the EB38. The structure-activity relationships in this compound series were developed by changes made on the benzyloxyphenyl group of the EB38, on the phenyl group attached to the 4th position of the isoxazole ring, on the methyl group at the 5th position and on the heterocyclic central ring. As a result, the isosteric changes on the central five-membered heterocyclic ring exemplified by Compound 36 with 1,5-diarylpyrazole ring elicited potent anticancer activity in all three cell lines compared to the lead compound EB38 (value of IC50 (Huh7)= 0.8, (MV)= 3.7 and (MCF7)= 1.5 μM). According to these results, it was determined that the replacement of the isoxazole center ring in the EB38 with the pyrazole ring significantly affected the anticancer activities and selectivity against different cancer cell lines. For this reason, subsequent synthesis studies continued with the pyrazole central ring, and modifications of the isoxazole derivatives were again introduced to the pyrazole analogues. In conclusion, 3,4-diaryl-isoxazole and 1,5-diaryl-pyrazole derivatives have been demonstrated as candidate compounds for further development as potential cancer therapeutics.