CYTOTOXIC ACTIVITY OF NEWLY SYNTHESIZED MOLECULAR HYBRIDS OF 2-THIOHYDANTOINS WITH ZINGERONE DERIVATIVES

Abstract

The cytotoxic activity of newly synthesized biologically active compounds, thiohydantoin hybrids of zingeron derivatives, was investigated in vitro on colon cancer cells HCT-116 and healthy lung fibroblast cells MRS-5. The effect of synthesized compounds on cell viability was examined by MTT test. Regarding the effect on viability of healthy MRC-5 cells, a moderate cytotoxic effect was observed only for the OMe derivative after prolonged exposure with IC5072h = 184.15 μM, which is comparable to the control (5-fluorouracil) with IC5072h = 181.71 μM. The cytotoxic potential of the tested compounds is time and dose dependent. The reduction in HCT-116 cell viability was achieved mainly after 72 hours at the highest applied concentration of test compounds. Based on the results, the OBu derivative showed the best antiproliferative activity on the HCT-116 cell line with IC5024h = 209.08 μM and IC5072h = 160.93 μM. 5-Fluorouracil showed a weaker cytotoxic effect with IC5024h = > 250 μM and IC5024h = 181.71 μM. This most active compound contains a butyl group as a substituent, so its activity is probably related to the lipophilicity of the substituent in the structure of the test molecule. The presented results indicate the potential of the tested compounds as anticancer agents without significant toxicity to healthy cell lines. The OBu derivative that showed the best activity is the leading candidate in the synthesized series. Its increased cytotoxicity compared to zingeron itself can be attributed to the introduction of the thiohydantoin nucleus into the molecule.