Anti-Inflammatory, Antiproliferative, and Radical-Scavenging Activities of Tolfenamic Acid and Its Metal Complexes
(EN)
Kovala-Demertzi, D.
(EN)
Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας
(EL)
Kovala-Demertzi, D.
(EN)
Some new complexes of tolfenamic acid (=2-[(2-methyl-3-chlorophenyl)amino]benzoic acid; Htolf) with potentially interesting biological activities are described. The complexes [Mn(tolf)(2)(H(2)O)(2)], [Co(tolf)(2)(H(2)O)(2)], [Ni(tolf(2)(H(2)O)(2)], [CU(tolf)(2)(H(2)O)](2), and [Zn(tolf)(2)(H(2)O)] were prepared by the reaction of tolfenamic acid, a potent anti-inflammatory drug, with metal salts. The radical-scavenging activities of the complexes were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging assay. Their ability to inhibit soybean lipoxygenase, beta-glucuronidase, and trypsin-induced proteolysis wits studied. Their inhibitory effects on rat paw edema induced by carrageenin was studied and compared with those of tolfenamic acid. The complex [Zn(tolf)(2)(H(2)O)] exhibited the strongest in vivo inhibitory effect at 0.1 mm/kg Body Weight (BW: 93.0 +/- 0.9%). superior than the inhibition induced by tolfenamic acid at the same molar dose (76.0 +/- 0.9%). Tolfenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines. MCF-7 (breast cancer cell line), T24 (bladder cancer cell line), and A-549 (non-small cell lung carcinoma), and a mouse fibroblast L-929 cell line. The complexes [Mn(tolf)(2)(H(2)O)(2)] and [Cu-(tolf)(2)(H(2)O)](2) have shown selectivity against T24 cell line. The IC(50) values of these two complexes against T24 cancer cell lines are in a micromolar range similar or better to that of the antitumor drug cisplatin.
(EN)