Thiosemicarbazides and their analogs are well known for their antifungal, antibacterial, antiviral and anticancer activity. We designed and synthetized a series of eight novel compounds representing several carbohydrate moieties linked via S-bridge with core anhydro template derived from levoglucosenone and functionalized at C-2 as thiosemicarbazides (namely FCP14, 14A, 15, 16, 16A, 20, 21 and 22). To evaluate the structure-activity relationships, all synthesized thiosemicarbazides were evaluated for their in vitro cytotoxic activity against seven cancer cell lines, brain (MO59J, MO59K), breast (MCF-7), cervix (HeLa), ovarian (A2782, A2780CIS) and colon (LoVo). Cancer cells were incubated in the presence of increased concentrations of glycosylated thiosemicarbazides or their analogs for 72h. Next, the cytotoxic properties of tested compounds were determined by evaluating the amount of living cells via colorimetric cell viability assay CCK-8. The most potent of the studied compounds were FCP20 and FCP21. They evoked concentration-dependent decreased cell viability on HeLa, A2780 and LoVo cells at concentrations up to 1mM. FCP16 and FCP16A showed moderate anticancer properties and FCP16A were shown to be considerably less cytotoxic than its analog (FCP16). FCP16 displayed significant anticancer activities against all seven tested cancer cell lines while FCP16A show cytotoxic properties only on HeLa, A22780 and A2780CIS cells. The remaining compounds (FCP22, FCP14, FCP14A and FCP15) didn’t induce a significant decrease in viability of all studied cancer cell lines. All results showed that the cytotoxic effect of glycosylated thiosemicarbazides and their analogs was structure and cancer cell line dependent. The data obtained clearly suggests that all functionalized thiosemicarbazides have the potential to augment or even replace current anticancer methods, however, their mechanism of action still must be evaluated.

Synthesis and cytotoxic effects of novel glycosylated thiosemicarbazides and their analogs as anticancer agents

252nd National Meeting (2016)

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