Anti-inflammatory, antiproliferative, and radical-scavenging activities of tolfenamic acid and its metal complexes.
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 was 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.
Kovala-Demertzi
Dimitra
D
Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, GR-45100 Ioannina. dkovala@cc.uoi.gr
Hadjipavlou-Litina
Dimitra
D
Primikiri
Alexandra
A
Staninska
Malgorzata
M
Kotoglou
Chronis
C
Demertzis
Mavroudis A
MA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008670:Metals / Q000737:chemistry*; D051379:Mice; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010851:Picrates / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D062367:ortho-Aminobenzoates / Q000737:chemistry / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D008670:Metals; D009942:Organometallic Compounds; D010851:Picrates; D062367:ortho-Aminobenzoates; C009500:tolfenamic acid; C004931:1,1-diphenyl-2-picrylhydrazyl