@misc{10481/68479,
year = {2021},
url = {http://hdl.handle.net/10481/68479},
abstract = {A series of diclofenac N-derivatives (2, 4, 6, 8c, 9c, 10a-c) were synthesized in order to test
their anti-cancer and anti-inflammatory effects. The anticarcinogen activity has been assayed against
three cancer cell lines: HT29, human colon cancer cells; Hep-G2, human hepatic cells; and B16-F10,
murine melanoma cells. First, we determined the cytotoxicity of the different compounds, finding
that the most effective compound was compound 8c against all cell lines and both compounds 4 and
6 in human Hep-G2 and HT29 cell lines. Compounds 4 and 8c were selected for the percentage of
apoptosis determination, cell cycle distribution, and mitochondrial membrane potential measure
because these products presented the lowest IC50 values in two of the three cancer cell lines assayed
(B16-F10 and HepG2), and were two of the three products with lowest IC50 in HT29 cell line.
Moreover, the percentages of apoptosis induction were determined for compounds 4 and 8c, showing
that the highest values were between 30 to 60%. Next, the effects of these two compounds were
observed on the cellular cycle, resulting in an increase in the cell population in G2/M cell cycle phase
after treatment with product 8c, whereas compound 4 increased the cells in phase G0/G1, by possible
differentiation process induction. Finally, to determine the possible apoptosis mechanism triggered
by these compounds, mitochondrial potential was evaluated, indicating the possible activation of
extrinsic apoptotic mechanism. On the other hand, we studied the anti-inflammatory effects of
these diclofenac (DCF) derivatives on lipopolysaccharide (LPS) activated RAW 264.7 macrophagesmonocytes murine cells by inhibition of nitric oxide (NO) production. As a first step, we determined
the cytotoxicity of the synthesized compounds, as well as DCF, against these cells. Then, sub-cytotoxic
concentrations were used to determine NO release at different incubation times. The greatest antiinflammatory effect was observed for products 2, 4, 8c, 10a, 10b, and 9c at 20 µg·mL−1
concentration
after 48 h of treatment, with inhibition of produced NO between 60 to 75%, and a concentration that
reduces to the 50% the production of NO (IC50 NO) between 2.5 to 25 times lower than that of DCF. In
this work, we synthesized and determined for the first time the anti-cancer and anti-inflammatory
potential of eight diclofenac N-derivatives. In agreement with the recent evidences suggesting that
inflammation may contribute to all states of tumorigenesis, the development of these new derivatives
capable of inducing apoptosis and anti-inflammatory effects at very low concentrations represent
new effective therapeutic strategies against these diseases.},
organization = {MINISTERIO DE ECONOMÍA Y COMPETITIVIDAD, PID2019-106222RB-C32/SRA (State Research Agency, 10.13039/501100011033)},
organization = {“Consejería de Economía, Conocimiento, Empresas y Universidad. Junta de Andalucía”, grant
number B1-BIO-281-UGR18},
publisher = {MDPI},
keywords = {Diclofenac},
keywords = {Anticancer activity},
keywords = {Anti-inflammatory activity},
keywords = {Nitric oxide},
keywords = {Drug development},
title = {Diclofenac N-Derivatives as Therapeutic Agents with Anti-Inflammatory and Anti-Cancer Effect},
doi = {10.3390/ijms22105067},
author = {Galisteo Pretel, Alberto and Jannus, Fatin and García García, Amalia and Aheget, Houssam and Rojas Macías, Sara and Lupiáñez Cara, José Antonio and Rodríguez Diéguez, Antonio and Reyes Zurita, Fernando Jesús and Quílez Del Moral, José Francisco},
}