Silver(I) complexes containing diclofenac and niflumic acid induce apoptosis in human-derived cancer cell lines.

We investigated the anti-cancer activity of [Ag(µ-dicl)]n 1 and [AgH(nif)2] 2 complexes against human cancer cell lines (MCF-7, HT-29, and HepG2) and mouse fibroblast (3T3-L1) cell line. Anti-proliferative activity was monitored by XTT cell viability and LDH leakage assays. Cell death mode was evaluated by multi-caspase activity, annexin V cytofluorimetric, MMP, cell cycle arrest, and ROS generation assays. Antioxidant capacity was evaluated on SOD, GPx, GR, and CAT enzymes. The XTT and LDH assay results showed that both complexes exhibited strong cytotoxicity against the tested cancer cell lines. The apoptotic mechanisms of the complexes were demonstrated by loss of MMP and increase in phosphatidylserine translocation, sub-G1 phase, and multi-caspase activity. Besides, both complexes induced the oxidative stress in MCF-7 cells by decreasing the activity of GPx, GR, and CAT enzymes. In conclusion, both Ag(I) complexes, especially 1, warrant for further in vivo evaluation as a new alternative in cancer treatment.HighlightsAg(I) complexes inhibited cell proliferation and induced LDH leakage in human cancer cell lines.Ag(I) complexes induced apoptosis through MMP disruption and ROS generation.Ag(I) complexes mimicked the multi-caspase activity.Ag(I) complexes increased the accumulation of sub-G1 phase.Ag(I) complexes inhibited the activity of antioxidant system enzymes.

In Vitro Anticancer Activity of Novel Co(II) and Ni(II) Complexes of Non-steroidal Anti-inflammatory Drug Niflumic Acid Against Human Breast Adenocarcinoma MCF-7 Cells.

Herein, we report the synthesis, characterization and anticancer activity of six novel complexes of non-steroidal anti-inflammatory drug niflumic acid with Co(II) and Ni(II). In vitro cytotoxicity screening in MCF-7, HepG2 and HT-29 cancer cell lines showed that the complex 3 [Co(nif)2(met)(4-pic)] and complex 6 [Ni(nif)2(met)(4-pic)] among all the complexes exhibited the highest cytotoxicity against MCF-7 cells with IC50 values of 11.14 µM and, 41.47 µM, respectively. Besides, all the complexes exhibited significantly higher selectivity towards mouse fibroblast 3T3L1 cells. Further mechanistic studies with both complexes on MCF-7 cells revealed their cytotoxic action through the mitochondrial-dependent apoptotic pathway causing an increase oxidative/nitrosative stress, decrease in mitochondrial membrane potential (ΔΨm), inducing the multicaspase activation and arresting the cell cycle at S phase. q-PCR analysis resulted in an increase in the expression of the apoptotic marker proteins bax, p53 and caspase-3 and -8 in MCF-7 cells, but a decrease in the expression of antiapoptotic bcl-2 gene. Moreover, both complexes induced the apoptosis through the inhibition of PI3K/Akt signaling pathway by decreasing the expression of PI3K and increasing dephosphorylation form of Akt protein. These results provide a significant contribution to the explanation of the anticancer mechanisms of these complexes in MCF-7 cells.

Synthesis, characterization, and in vitro effect of the Cu(II) complex with niflumic acid and 3-picoline on paraoxanase-I.

Niflumic acid is used to treat inflammatory rheumatoid diseases, pain, and fever. The present study reports the experimental, spectroscopic, thermal, structural analyses, and biological activities of this complex. The nonsteroidal anti-inflammatory drug niflumic acid, 3-picoline, and copper(II) chloride were utilized to synthesize a new complex: [Cu2 Cl 2 (nif) 2 (3-pic) 4 ]. The crystal structure of [Cu 2 Cl 2 (nif) 2 (3-pic) 4 ] was determined by X-ray crystallography. The complex crystallizes in the triclinic space group P-1 and each Cu(II) center displayed six-coordinated distorted octahedral geometry. Two Cu(II) centers are connected by a chloro-bridge to form the binuclear metal core. Finally, the in vitro effects of the synthesized new complex and free niflumic acid were evaluated on the human serum paraoxonase 1 enzyme. At low doses, both the new complex and free niflumic acid showed very good inhibition activity with different inhibition mechanisms. In addition, the results showed that the new complex has more inhibition activity than free niflumic acid.

Synthesis and characterization of four novel palladium(II) and platinum(II) complexes with 1-(2-aminoethyl)pyrrolidine, diclofenac and mefenamic acid: In vitro effect of these complexes on human serum paraoxanase1 activity.

In this study, the effects of four novel mononuclear palladium(II) and platinum(II) complexes on the activity of human serum paraoxanase1 were examined. First, four novel mononuclear palladium(II) and platinum(II) complexes were synthesized with a nitrogen donor ligand 1-(2-aminoethyl)pyrrolidine and nonsteroidal anti-inflammatory drugs diclofenac, mefenamic acid. These complexes were characterized by spectroscopic, thermal, and elemental analyses. The crystal structures of complex [Pd(2-amepyr)2 ](dicl)2 1 and [Pd(2-amepyr)2 ](mef)2 3 were determined by X-ray crystallography. Then, paraoxonase1 enzyme was purified from human serum. The effects of these complexes on enzyme were evaluated in vitro. The complexes consist of the cationic unit and the counterions. The diclofenac and mefenamic acid acted as a counterion in the complexes. It was observed that all the complexes were stable up to high temperatures. These complexes, even at low doses, inhibited the activity of the enzyme with different inhibition mechanisms.