Trinuclear silver(I) complex of non-steroidal anti-inflammatory drug naproxen: Synthesis, characterization, and in vitro cytotoxicity

Abstract

Herein, a new silver(I) complex with the non-steroidal anti-inflammatory drug naproxen and nitrogen donor 3-picoline ligands was synthesized, characterized, and subsequently tested for its cytotoxicity against different types of cancer cell lines. Elemental analysis, Fourier transform infrared spectroscopy, thermal, and proton nuclear magnetic resonance techniques showed that the molecular formula of the prepared complex is bis(3-picoline)tris(-naproxenato)trisilver(I) and naproxen ligands bind to silver ions in a bridging bidentate mode. 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) results revealed that silver salts and naproxen alone showed quite weak cytotoxic activity against human breast adenocarcinoma (MDA-MB-453), lung adenocarcinoma (A-549), and colorectal adenocarcinoma (HT-29) cell lines (IC50 > 250 µM), whereas the complex displayed dose dependent cytotoxicity against the aforementioned cell lines. The highest cytotoxicity was observed on MDA-MB-453 cells with an IC50 value of 11.73 µM. Moreover, the complex showed higher selectivity against the cancer cell lines compared to fibroblast 3T3-L1 cells. This study provides preliminary scientific data on the complex for further elucidation of its anticancer mechanism of action.

Silver(I) Complexes with Mefenamic Acid and Nitrogen Heterocyclic Ligands: Synthesis, Characterization, and Biological Evaluation

“…Hence, A549 cells were selected to further test the activity of complex 1 in the following experiments. Complex 1 has better antitumor activity, probably because its hydrophobicity is the strongest among the four compounds, which enables 1 to cross the cell membrane more easily. , The cytotoxicity of complex 1 to the A549 cell line is higher than that of the six reported Ag­(I)–NSAID complexes, but complexes 2 , 3 , and 4 exhibit less toxicity to A549 cells than those six compounds. − Complex 1 displays stronger activity against the HepG-2 cancer cells compared with [AgH­(nif) 2 ], [Ag­(tpp) 2 (tolf)], and [Ag­(tpp) 2 (ibu)]; however, the four complexes ( 1 , 2 , 3 , and 4 ) show lower cytotoxicity in HepG-2 than other silver­(I) compounds of nonsteroid anti-inflammatory drugs. ,,− Complexes 1 , 2 , 3 , and 4 have relatively low toxicity toward MCF-7 cells, and their IC 50 values are less than those of the previously reported silver­(I)–NSAID complexes. ,,,− …”

“…27−29 Recently, metal complexes based on NSAIDs have gained great interest, and they are often more active than free NSAIDs. [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]47,[80][81][82][83]86 Mefenamic acid (Hmef), a nonsteroidal anti-inflammatory drug, is used as an effective analgesic and antipyretic. Several research groups have reported metal complexes with mefenamic acid as ligands and have evaluated their biological activities.…”

“…However, the use of platinum-based drugs has been limited because of their side effects and drug resistance . To enhance cancer treatment and overcome the drawbacks associated with platinum-based drugs, nonplatinum metal complexes have been studied and suggested as potential alternatives for cancer treatment. − However, among the nonplatinum metal complexes, complexes of ruthenium, iron, copper, rhenium, osmium, iridium, palladium, rhodium, gold, and silver have received attention widely. , Recent research has shown that many silver­(I) complexes exhibit significant anticancer efficacy as potential anticancer drugs. − ,,,,− Some silver­(I) complexes exhibit significant in vitro anticancer activity, surpassing that of cisplatin. ,− ,,,,,,− Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain, inflammation, and fever . The primary function of NSAIDs is to block the production of prostaglandins through the inhibition of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) .…”

“…Therefore, NSAIDs are used as promising chemopreventive agents for cancer . Moreover, some NSAIDs may exhibit synergistic anticancer effects with diverse anticancer drugs, − and some NSAIDs have shown anticancer activity. − Recently, metal complexes based on NSAIDs have gained great interest, and they are often more active than free NSAIDs. − ,,− , Mefenamic acid (Hmef), a nonsteroidal anti-inflammatory drug, is used as an effective analgesic and antipyretic. Several research groups have reported metal complexes with mefenamic acid as ligands and have evaluated their biological activities. ,− ,, Several silver­(I) complexes with the mefenamato ligand have been identified in the reported metal complexes of mefenamic acid with significant anticancer activity. ,, …”

In Vitro Cytotoxic Evaluation of a Silver(I) Complex Including Non-Steroidal Anti-Inflammatory Drug Niflumic Acid and 3-Picoline on Human-Derived Cancer Cell Lines

“…One of the necessary parameters to be considered in cytotoxicity studies is the selectivity of the test agents between cancer and healthy cells [32][33][34]. In this context, as seen in Table 1, the [Ag(nif)(3-pic)] complex displayed much higher selectivity on cancer cells when compared to normal cells, and the highest selectivity was determined against HT-29 cells with an SI value of 4.67, followed by MDA-MB-453 (SI: 3.82) and A-549 (SI: 2.74) cells, respectively.…”