Iron(II)-cyclopentadienyl compounds are cytotoxic against colon adenocarcinoma cell lines: Ethylenebis(diphenylphosphane) vs. triphenylphosphane

Adhan Pilon; Fernando Avecilla; Bálint Rácz; Gerda T Gátszegi; Gabriella Spengler; M Paula Robalo; Éva A Enyedy; M Helena Garcia; Andreia Valente

doi:10.1016/j.jinorgbio.2023.112386

Iron(II)-cyclopentadienyl compounds are cytotoxic against colon adenocarcinoma cell lines: Ethylenebis(diphenylphosphane) vs. triphenylphosphane

J Inorg Biochem. 2023 Dec:249:112386. doi: 10.1016/j.jinorgbio.2023.112386. Epub 2023 Sep 26.

Authors

Adhan Pilon¹, Fernando Avecilla², Bálint Rácz³, Gerda T Gátszegi⁴, Gabriella Spengler³, M Paula Robalo⁵, Éva A Enyedy⁶, M Helena Garcia¹, Andreia Valente⁷

Affiliations

¹ Centro de Química Estrutural, Institute of Molecular Sciences and Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
² Universidade da Coruña, Grupo NanoToxGen, Centro Interdisciplinar de Química y Biología (CICA), Departamento de Química, Facultade de Ciencias, Campus de A Coruña, 15071 A Coruña, Spain.
³ Department of Medical Microbiology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, H-6725 Szeged, Hungary.
⁴ Department of Medical Microbiology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, H-6725 Szeged, Hungary; MTA-SZTE Lendület Functional Metal Complexes Research Group, Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary.
⁵ Centro de Química Estrutural, Institute of Molecular Sciences, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; Departamento de Engenharia Química, Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, Av. Conselheiro Emídio Navarro, 1, 1959-007 Lisboa, Portugal.
⁶ MTA-SZTE Lendület Functional Metal Complexes Research Group, Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary.
⁷ Centro de Química Estrutural, Institute of Molecular Sciences and Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal. Electronic address: amvalente@fc.ul.pt.

PMID: 37827090
DOI: 10.1016/j.jinorgbio.2023.112386

Abstract

Structure-activity studies aiming to understand the role of each coligand in the formulation of new metallodrugs is an important subject. In that frame, six new compounds with general formula [Fe(η⁵-C₅H₅)(dppe)(L)][CF₃SO₃] with L = benzonitriles (1-4) or carbon monoxide (5) and compound [Fe(η⁵-C₅H₅)(CO)(PPh₃)₂][CF₃SO₃] (6) were synthesized and compared with three other previously reported compounds [Fe(η⁵-C₅H₅)(CO)(L)(PPh₃)][CF₃SO₃]. We were particularly interested in assessing the effect of dppe vs. (PPh₃ + CO) for this set of compounds. For that, all compounds were tested against two human colon adenocarcinoma cell lines, Colo205 and the refractile Colo320 (expressing ABCB1, an efflux pump causing multidrug resistance), showing IC₅₀ values in the micromolar range. The presence of dppe in the compound's coordination sphere over (PPh₃ + CO) allows for more redox stable compounds showing higher cytotoxicity and selectivity, with improved cytotoxicity towards resistant cells that is not related to the inhibition of ABCB1. Further studies with GSH and H₂O₂ for selected compounds indicated that their antioxidant ability is not probably the main responsible for their cytotoxicity.

Keywords: ABCB1; Anticancer; Colon adenocarcinoma; Iron(II)-cyclopentadienyl; Metallodrugs; Redox activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma*
Antineoplastic Agents* / pharmacology
Cell Line, Tumor
Colonic Neoplasms* / drug therapy
Ferrous Compounds / pharmacology
Humans
Hydrogen Peroxide
Iron

Substances

tesmilifene
Iron
Hydrogen Peroxide
Antineoplastic Agents
Ferrous Compounds