Ruthenium(II) polypyridyl complexes with benzothiophene and benzimidazole derivatives: Synthesis, antitumor activity, solution studies and biospeciation.

Autor: Dömötör O; Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary; MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary. Electronic address: domotor.o@chem.u-szeged.hu., Teixeira RG; Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1049-016 Lisboa, Portugal., Spengler G; MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary; Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary., Avecilla F; Universidade da Coruña, Grupo NanoToxGen, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Química, Facultade de Ciencias, Campus de A Coruña, 15071A Coruña, Spain., Marques F; Centro de Ciências e Tecnologias Nucleares and Departamento de Ciências e Engenharia Nucleares, Instituto Superior Técnico, Universidade de Lisboa, EN 10 (km 139,7), 2695-066 Bobadela, Loures, Portugal., Lenis-Rojas OA; Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1049-016 Lisboa, Portugal., Matos CP; Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1049-016 Lisboa, Portugal., de Almeida RFM; Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1049-016 Lisboa, Portugal., Enyedy ÉA; Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary; MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary., Tomaz AI; Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1049-016 Lisboa, Portugal. Electronic address: aidiniz@fc.ul.pt.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2023 Jan; Vol. 238, pp. 112058. Date of Electronic Publication: 2022 Nov 02.
DOI: 10.1016/j.jinorgbio.2022.112058
Abstrakt: With the aim to incorporate pharmacophore motifs into the Ru(II)-polypyridyl framework, compounds [Ru(II)(1,10-phenantroline) 2 (2-(2-pyridyl)benzo[b]thiophene)](CF 3 SO 3 ) 2 (1) and [Ru(II)(1,10-phenantroline) 2 (2-(2-pyridyl)benzimidazole)](CF 3 SO 3 ) 2 (2) were prepared, characterized and tested for their antitumor potential. The solid-state structure of the compounds was confirmed by single-crystal X-ray diffraction analysis. The solution behavior of both complexes was investigated, namely their solubility, stability, and lipophilicity in physiological mimetic conditions, as well as an eventual uptake by passive diffusion. In vitro anticancer activity of the complexes on ovarian and different colon cancer cells and apoptosis induction by the complexes were studied. A slow transformation process was observed for complex 1 in aqueous solution when exposed to sunlight, while complex 2 undergoes deprotonation (pK a  = 7.59). The lipophilicity of this latter complex depends strongly on the pH and ionic strength. In contrast, 1 is rather hydrophilic under various conditions. Complex 1 was highly cytotoxic on Colo-205 human colon (IC 50  = 7.87 μM) and A2780 ovarian (IC 50  = 2.2 μM) adenocarcinoma cell lines, while 2 displayed moderate anticancer activity (30.9 μM and 18.0 μM, respectively). The complexes induced late apoptosis and necrosis. Only a weak binding of the complexes to human serum albumin, the main transport protein in blood serum, was found. However, a more significant binding to calf thymus DNA was observed in UV-visible titrations and fluorometric dye displacement studies. Detailed analysis of fluorescence lifetime data collected for the latter systems reveals not only the partial intercalation of the complexes, but goes beyond the usual simplified interpretations.
Competing Interests: Declaration of Competing Interest There are no conflicts to declare.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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