Curcumin (diferuloylmethane) represents a polyphenol extracted from the plant Curcuma longa which has attracted the attention of scientists for medicinal purposes. In this context, we obtained 5 different derivates in order to test their anti-tumoral effect on human cervix cancer. In this context, we obtained five curcumin derivatives, two have the structure similar with two of the natural compounds, diferuloylmethane (D4), respectively p,p-dihydroxydicinnamoylmethane (D3) and the other three have modified structures with amide or amino groups (D1, D2 and D3). The compounds were synthesized in the microwave field and characterized by ¹H-NMR and ¹³C-NMR spectroscopy, UV-Vis and infrared spectroscopy, fluorescence and thermal analysis. Their biocompatibility was investigated on human fibroblast lung cells (MRC-5 cell line) and the anti-tumoral effect was tested on human cervix cancer cells (HeLa cell line) after 24 and 72 hours of incubation with concentrations up to 500 μg/mL of derivates. D1 and D2 derivatives decreased the number of viable tumor cells in a dose-dependent manner, and concentrations up to 200 μg/mL of these samples did not alter the viability of normal lung fibroblasts until 72 h of incubation. In addition, increased nitric oxide levels released in the cell culture media were noticed only for doses higher than 50 μg/mL. In the case of D5 sample, no changes were observed for both types of cell lines regardless the time of incubation or doses used. D3 and D4 samples killed almost all HeLa cells after the incubation with doses equal or higher than 50 μg/mL. This antitumor effect was very well correlated with an increased level of nitric oxide. However, the high doses of curcumin derivatives induced death of non-tumoral cells and must be avoided in future experiments. In conclusion, the outcomes of our study performed in vitro revealed that curcumin derivates posed minimal toxicity towards normal lung cells and the anti-proliferative efficiency results experimentally shown on cancer cells seem very promising to be further translated on in vivo studies and human clinical trials which are limited for this moment.

Acknowledgments This work was supported by a grant of the Romanian Ministry of Research and Innovation, CCCDI – UEFISCDI, project number PN-III-P2-2.1-PED-2019-1471, within PNCDI III.