Cytotoxicity Evaluation of Unmodified Paddlewheel Dirhodium(II,II)-Acetate/-Formamidinate Complexes and Their Axially Modified Low-Valent Metallodendrimers

Molecules. 2023 Mar 15;28(6):2671. doi: 10.3390/molecules28062671.

Abstract

Two diphenyl formamidine ligands, four dirhodium(II,II) complexes, and three axially modified low-valent dirhodium(II,II) metallodendrimers were synthesized and evaluated as anticancer agents against the A2780, A2780cis, and OVCAR-3 human ovarian cancer cell lines. The dirhodium(II,II) complexes show moderate cytotoxic activity in the tested tumor cell lines, with acetate and methyl-substituted formamidinate compounds displaying increased cytotoxicity that is relative to cisplatin in the A2780cis cisplatin resistant cell line. Additionally, methyl- and fluoro-substituted formamidinate complexes showed comparable and increased cytotoxic activity in the OVCAR-3 cell line when compared to cisplatin. The low-valent metallodendrimers show some activity, but a general decrease in cytotoxicity was observed when compared to the precursor complexes in all but one case, which is where the more active acetate-derived metallodendrimer showed a lower IC50 value in the OVCAR-3 cell line in comparison with the dirhodium(II,II) tetraacetate.

Keywords: cytotoxicity; dirhodium(II,II); formamidine; metallodendrimers; metallodrug.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis
  • Cell Line, Tumor
  • Cisplatin / therapeutic use
  • Coordination Complexes* / pharmacology
  • Coordination Complexes* / therapeutic use
  • Female
  • Humans
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / pathology

Substances

  • Cisplatin
  • Antineoplastic Agents
  • Coordination Complexes

Grants and funding

This research was funded by University of Cape Town (UCT) and the Department of Science and Technology of South Africa; Romanian National Authority for Scientific Research and Innovation UEFISCDI project PN-III-P4-ID-PCE-2021-1572; the Romanian-South African Bilateral Cooperation grant PNIII-P3-116; and the National Research Foundation of South Africa (UID: 104023 and UID: 11768). The APC was funded by UCT URC Open Access Journal Publication Fund.