Manganese(I) tricarbonyl complexes as potential anticancer agents

Oscar A. Lenis-Rojas, Beatriz Carvalho, Rui Cabral, Margarida Silva, Sofia Friães, Catarina Roma-Rodrigues, Marta S. H. Meireles, Clara S. B. Gomes, Jhonathan A. A. Fernández, Sabela F. Vila, Juan A. Rubiolo, Laura Sanchez, Pedro V. Baptista, Alexandra R. Fernandes, Beatriz Royo

Research output: Contribution to journalArticlepeer-review

Abstract

The antiproliferative activity of [Mn(CO)3(N^N)Br] (N^N = phendione 1, bipy 3) and of the two newly synthesized Mn complexes [Mn(CO)3(acridine)(phendione)]OTf (2) and [Mn(CO)3(di-triazole)Br] (4) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), HCT116doxR (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The antiproliferative assay showed a dose-dependent effect higher in complex 1 and 2 with a selectivity toward ovarian carcinoma cell line 21 times higher than in human fibroblasts. Exposure of A2780 cells to IC50 concentrations of complex 1 and 2 led to an increase of reactive oxygen species that led to the activation of cell death mechanisms, namely via intrinsic apoptosis for 2 and autophagy and extrinsic apoptosis for 1. Both complexes do not target DNA or interfere with cell cycle progression but are able to potentiate cell migration and neovascularization (for 2) an indicative that their application might be directed for initial tumor stages to avoid tumor invasion and metastization and opening a new avenue for complex 2 application in regenerative medicine. Interestingly, both complexes do not show toxicity in both in vivo models (CAM and zebrafish). Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish
JournalJournal of Biological Inorganic Chemistry
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • A2780 tumor cells
  • Antiproliferative activity
  • Cancer
  • In vivo models
  • Mn(I) complexes

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