IN VITRO AND IN SILICO CYTOTOXICITY EVALUATION OF SOME ISATIN MANNICH BASES ON HUMAN MELANOMA CELLS

OpenAlex İngilizce

Mannich bases tend to suppress cell proliferation in damaged tissues because of particular metal chelation properties. Amine components of isatin mannich bases - piperidine (P1), morpholine (P2) and N-methyl piperazine (P3) – were evaluated for their cytotoxicity potentials on melanoma cells. P1, P2 and P3 products were purified using crystallization and characterized by NMR. Human melanoma cells (G361) were produced in DMEM medium including 10% FBS, 1% penicillin/streptomycin at 37°C and 5% CO2 conditions. Compounds were applied to medium containers separated to 24 pieces plates as 1x105 melanoma cells/well for 24 hours. Expression levels of caspase-3, p53 and β-actin were investigated from RNA samples by qRT-PCR. Mannich bases were efficient at 20, 20 and 50 μg/ml concentrations for P1, P2 and P3, respectively. P2 (20 μg/ml) showed the highest cytotoxic effect with 92 percent. The most significant increase in p53 gene expression was carried out by P2 product with 6.78 fold compared to control group. P2 also upregulated caspase-3 expression by 9.72 fold. Newly synthesized Mannich bases, especially P2, were found to have antitumor potential. Moreover, molecular docking studies revealed that P2 is a potent allosteric activator of caspase-3. However, there is need for in vivo trials and extensive researches to fully elucidate the molecular bioefficacies of these molecules.