SÍNTESIS DE UN ANÁLOGO DE LA L-ORNITINA Y SU EFECTO SOBRE CÉLULAS NEOPLÁSICAS EN CULTIVO

Abstract

Polyamines are essential for tissue differentiation, cell growth and cell division processes. Enzyme inhibition is a strategy used to develop new chemotherapeutic agents. For this reason, inhibition of metabolism of polyamines (PAA) has been selected as a possible target for cancer chemotherapy. Currently, more potent and selective inhibitors of the metabolism of polyamines are being developed, that are less toxic, which can pass through cell membranes and whose metabolism and excretion is not very fast. We know a considerable number of compounds that are capable of reducing ODC activity in cells, however, -difluoromethyl-ornithine is the only inhibitor of ODC, which has survived preclinical and preliminary clinical trials as treatment in cancer chemotherapy, although one of its main drawbacks is its toxicity and accelerated metabolism. Enzymology Laboratory from Department of Biochemistry, ENCB-IPN is working on the design, synthesis and study of antineoplastic agents that are ODC enzyme inhibitors. So, in this study it was synthesized and evaluated the 2.2- diphenyl-1,3,2-oxazaborolidine-5-one of the L-ornithine (DFOXBO), as a potential antineoplastic agent on in vitro cancer cells. The DFOXBO was characterized by infrared spectroscopy and nuclear magnetic resonance of 1H, 13C and 11B. It was determined the effect of DFOXBO on the survival and proliferation of cell lines: Vero cells (control non-neoplastic) cells and HeLa cells (cervical carcinoma). Cytotoxicity experiments showed that DFOXBO caused cytotoxic effects in concentration and time dependant manner in HeLa cells, with EC50 value of 10 μM>EC50<50 μM and practically did not affect the viability of Vero cells. Putrescine partially reversed the cytotoxic effect of DFOXBO, suggesting that the cytotoxic effect produced it was by inhibition of ODC. Besides, DFOXBO caused inhibition of cell proliferation in a concentration-dependant manner in HeLa cells, with a slight antiproliferative effect on control Vero cells. According to the above, the DFOXBO has expectations to continue studying and possibly in the future, to make it used in the treatment of cancer and other proliferative diseases.