Abstract

Rana Al-Kerm40101, Rola Al-Kerm40102, Othman Hamed40103*, Ashraf Swaft40104, Mohammad Qneibi40105, Avni Berisha40106, Omar Dagdage40107 and Ghaleb Adwan40109

Developing a new effective anticancer agent becomes an urgent need to overcome of current drug-resistance. In this study, we demonstrated that curcumin with heterocyclic moiety can function as an anticancer agent in a human. A new series of curcumin-based benzodiazepines, diazepines and diazoles were prepared using a simple one pot process. The process involved a condensation reaction of curcumin with various 1,2 diamino compounds and hydrazine. The structures of the prepared heterocycles were identified by the spectroscopic methods Fourier-Transform Infrared Spectroscopy (FT-IR), ¹H NMR (Proton Nuclear Magnetic Resonance), and ¹³C NMR. The in vitro anticancer activities of the synthesized curcumin-based heterocycles against HeLa cancer cells were evaluated by the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The viability of HeLa cells was reduced in the range of 4.48%-14.57% within the studied concentrations. Curcumin-based diazepine 6 showed the highest cytotoxic effect on the HeLa cells at all concentrations. It reduced the viability of the tested HeLa cells in range of 4.48% for the 400 μg/ml concentration to 4.95% for the 12.5 μg/ml concentration. Moreover, heterocyclic 6 showed the highest cytotoxic and cytostatic effect among the tested heterocyclics against HeLa cells. It exhibited IC₅₀ (Half-maximal inhibitory concentration) and a cytostatic effect of 0.4572 and 0.08515 μg/ ml, respectively at a nontoxic level, as the control L6 cells showed cytotoxic and cytostatic effect with IC₅₀ values of 22.47 and 1.977 μg/ml, respectively. This study revealed that, the prepared curcumin-based compounds exhibit a promising anticancer activity against HeLa cancer cells at a nontoxic concentration.