Pd()/diphosphine/curcumin complexes as potential anticancer agents

• Published in: Dalton transactions : an international journal of inorganic chemistry 2024-12, Vol.53 (47), p.1892-18916
• Main Authors: Dutra, Jocely L, Honorato, João, Graminha, Angélica, Moraes, Carlos André F, de Oliveira, Kleber T, Cominetti, Marcia R, Castellano, Eduardo E, Batista, Alzir A
• Format: Article
• Language: English
• Subjects: Anticancer properties; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cancer; Cell cycle; Cell death; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemical analysis; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Crystallography; Curcumin - chemistry; Curcumin - pharmacology; Cytotoxicity; Drug Screening Assays, Antitumor; Ethane; Humans; Ligands; Lungs; Molecular Structure; Natural products; NMR; Nuclear magnetic resonance; Ovaries; Palladium; Palladium - chemistry; Palladium - pharmacology; Phosphines; Phosphines - chemistry; Phosphines - pharmacology; Toxicity; Tumors
• ISSN: 1477-9226; 1477-9234; 1477-9234
• DOI: 10.1039/d4dt01045k

Palladium( ii ) complexes have stimulated research interest mainly due to their in vitro cytotoxicity against various cancer cell lines and their low cytotoxicity in healthy cells. Thus, in this work, we combined Pd( ii )/phosphine systems with the natural product curcumin as a ligand, obtaining a series of complexes, [Pd(cur)(PPh 3 ) 2 ]PF 6 ( A1 ), [Pd(cur)(dppe)]PF 6 ( A2 ), [Pd(cur)(dppp)]PF 6 ( A3 ), [Pd(cur)(dppb)]PF 6 ( A4 ) and [Pd(cur)(dppf)]PF 6 ( A5 ), where dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, dppb = 1,4-bis(diphenylphosphino)butane, and dppf = 1,1′-bis(diphenylphosphino)ferrocene (P-P), which were characterized by elemental analysis, molar conductivity analysis, and mass, NMR ( 1 H, 13 C, 31 P{ 1 H}), UV-vis, and IR spectroscopies, and four of them ( A1 , A2 , A4 , and A5 ) by X-ray crystallography. The in vitro cell viability of the complexes A1-A5 , cisplatin, and the free ligand curcumin against MDA-MB-231 (human triple-negative breast tumor cells), SK-BR-3 (human breast tumor cells), A549 (human lung tumor cells), MRC-5 (non-tumor human lung cells), A2780 (human ovarian carcinoma cells), and A2780cis (cisplatin-resistant human ovarian carcinoma cells), was evaluated by the MTT colorimetric assay. For the tumor cell lines tested, the complexes showed good anticancer activities. The results showed that in general the complexes had lower IC 50 values than free curcumin and the precursors [PdCl 2 (P-P)]. IC 50 results obtained for the A1-A5 complexes, in the MCF-7 cell line, are similar to those that had already been observed for some Pd/bipy/curcumin complexes. In the MDA-MB-231 cell line, complexes A1 and A5 stood out, with their lowest IC 50 values, around 5 μmol L −1 , and the complexes appeared to be more active (lower IC 50 values) against the ovarian cell lines. Complex A1 was 23 and 22-fold more cytotoxic than cisplatin, against the A2780 and A2780cis cells, respectively. The complex A1 was studied on A2780cis cells and it was found that this complex inhibits colony formation and induces cell cycle arrest in the sub-G1 phase in a concentration-dependent manner and leads to cell death by apoptosis. The DCFDA assay revealed a potent ROS induction for complex A1 . Palladium( ii ) complexes have stimulated research interest mainly due to their in vitro cytotoxicity against various cancer cell lines and their low cytotoxicity in healthy cells.