Anti‐tumor platinum (IV) complexes bearing the anti‐inflammatory drug naproxen in the axial position

Abstract

The role of inflammation in cancer generation is gaining importance in the field of cancer research. The chemo‐anti‐inflammatory strategy that involves using non‐steroidal anti‐inflammatory drug compounds as effective anti‐tumor agents is being acceded globally. In the present study, seven new Pt (IV) complexes based on cisplatin, carboplatin and oxaliplatin scaffold bearing the anti‐inflammatory drug naproxen in the axial position were synthesized and characterized by elemental analysis, ESI‐MS, Fourier transform‐infrared, 1H‐ and 195Pt‐NMR spectroscopy. The reduction behavior in the presence of ascorbic acid was studied using high‐performance liquid chromatography. The cytotoxicity against two human breast cell lines and the anti‐inflammatory properties were evaluated. All the complexes are able to promote a comparable activity, with average three‐ and 13‐fold more cytotoxic than cisplatin against MCF7 and MDA‐MB‐231 cell lines, respectively. The complexes show remarkable anti‐inflammatory effects, which indicated their potential in treating cancer associated with inflammation and reducing side‐effects of chemotherapy.

Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX‐2 and PD‐L1

“…DNP is soluble in a range of organic solvents such as methanol, dimethylformamide (DMF), and dimethylsulfoxide (DMSO), but is almost insoluble in water. NP was prepared and characterized as reported in the literature [37] …”

“…NP was prepared and characterized as reported in the literature. [37] Thel ipophilicity of the complexes was evaluated by measuring their octanol-water partition coefficients.T he lipophilicity parameter (log P O/W )o fD NP and NP was determined to be 1.46 and 0.02, respectively (Table S1), indicating that they are more lipophilic than CDDP (log P O/W = À2.35). In general, the lipophilicity of acompound positively correlates with its passive diffusion through the cellular membrane.D NP is more lipophilic than NP and CDDP,i mplying that it may penetrate the cell membrane more readily and have ahigher cellular accumulation than NP and CDDP.E vidently,N PX moiety could improve the lipophilicity.…”

“…Fort he sake of comparison, Pt IV complex with one axial NPX ligand, namely NP,w as also prepared and investigated. In fact, the anticancer and antiinflammatory activities of NP have been studied recently; [37,38] however, DNP has not been reported so far.…”

Antiproliferative Activity of Pt(IV) Conjugates Containing the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Ketoprofen and Naproxen †

“…This improvement is well-known in organic chemistry, but it has been seldom reported in the syntheses of Pt(II) and Pt(IV) complexes [39,40,41,42]. The synthesis of complex 3 has been already reported in the literature, but this was done with a different procedure [35].…”

“…Following this research, several cisplatin-, oxaliplatin-, or kiteplatin-based Pt(IV) complexes containing NSAIDs (i.e., indomethacin, ibuprofen, flurbiprofen, naproxen, and wogonin) as axial ligands have been reported in literature [27,28,29,30,31,32,33,34,35].…”