DESIGN, SYNTHESIS AND CYTOTOXIC EVALUATION OF NOVEL BUTANOIC ACID DERIVATIVES

Cancer is now one of the world's most deadly diseases. According to the American Cancer Society, 2 million people in the US are diagnosed with cancer and 600,000 people will die from cancer in 2024. Breast, liver and lung cancer are among the most common cancers worldwide. Many challenges need to be overcome when treating Cancer. These include the destructive effect of long-term treatment on the patient, side effects of existing drugs and drug resistance. To overcome these problems, the synthesis of 4-oxo-4-(4-(2-oxo-2-(2-(substituted carbamothioil)hydrazinyl) ethoxy)phenyl)phenyl)butanoic acid derivatives was designed and activity studies were performed. Nuclear magnetic resonance (NMR) spectroscopy was used for structural analysis of the resulting compounds (3a-3f). Cytotoxicity studies of the synthesized compounds were carried out on NIH3T3 (healthy mouse embryonic fibroblast) and A549 (human lung carcinoma) cell lines. The IC50 values of compounds 3e and 3f were determined to be 8.495±0.367 μM and 10.248±0.161 μM, respectively. In addition, compound 3f was found to have the selective cytotoxic activity against cancer cells. In silico studies showed that 3e and 3f interacted with the allosteric cavity of the caspase-3 enzyme. Both showed similar localization on the enzyme surface. Their substitution was in interaction with ARG64, ARG207 and GLN161 residues. Based on these findings, both compounds have a potential anticancer activity profile with cytotoxic selectivity.