| dc.description.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. | |
