Conjugates Containing Two and Three Trithiolato-Bridged Dinuclear Ruthenium(II)-Arene Units as In Vitro Antiparasitic and Anticancer Agents

Valentin Studer; Nicoleta Anghel; Oksana Desiatkina; Timo Felder; Ghalia Boubaker; Yosra Amdouni; Jessica Ramseier; Martin Hungerbühler; Christoph Kempf; Johannes Thomas Heverhagen; Andrew Hemphill; Nico Ruprecht; Julien Furrer; Emilia Păunescu

doi:10.3390/ph13120471

journal article Open Access Dec 16, 2020

Conjugates Containing Two and Three Trithiolato-Bridged Dinuclear Ruthenium(II)-Arene Units as In Vitro Antiparasitic and Anticancer Agents

Valentin Studer Nicoleta Anghel Oksana Desiatkina Timo Felder

Ghalia Boubaker Yosra Amdouni

Jessica Ramseier Martin Hungerbühler

Christoph Kempf Johannes Thomas Heverhagen Andrew Hemphill

Nico Ruprecht

Julien Furrer

Emilia Păunescu

Pharmaceuticals Vol. 13 No. 12 pp. 471 · MDPI AG

View at Publisher Save 10.3390/ph13120471

Abstract

The synthesis, characterization, and in vitro antiparasitic and anticancer activity evaluation of new conjugates containing two and three dinuclear trithiolato-bridged ruthenium(II)-arene units are presented. Antiparasitic activity was evaluated using transgenic Toxoplasmagondii tachyzoites constitutively expressing β-galactosidase grown in human foreskin fibroblasts (HFF). The compounds inhibited T.gondii proliferation with IC50 values ranging from 90 to 539 nM, and seven derivatives displayed IC50 values lower than the reference compound pyrimethamine, which is currently used for treatment of toxoplasmosis. Overall, compound flexibility and size impacted on the anti-Toxoplasma activity. The anticancer activity of 14 compounds was assessed against cancer cell lines A2780, A2780cisR (human ovarian cisplatin sensitive and resistant), A24, (D-)A24cisPt8.0 (human lung adenocarcinoma cells wild type and cisPt resistant subline). The compounds displayed IC50 values ranging from 23 to 650 nM. In A2780cisR, A24 and (D-)A24cisPt8.0 cells, all compounds were considerably more cytotoxic than cisplatin, with IC50 values lower by two orders of magnitude. Irrespective of the nature of the connectors (alkyl/aryl) or the numbers of the di-ruthenium units (two/three), ester conjugates 6–10 and 20 exhibited similar antiproliferative profiles, and were more cytotoxic than amide analogues 11–14, 23, and 24. Polynuclear conjugates with multiple trithiolato-bridged di-ruthenium(II)-arene moieties deserve further investigation.

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Details

Published: Dec 16, 2020
Vol/Issue: 13(12)
Pages: 471
License: View

Authors

V

Valentin Studer

Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland

N

Nicoleta Anghel

Vetsuisse Faculty, Institute of Parasitology, University of Bern, Länggassstrasse 122, CH-3012 Bern, Switzerland

O

Oksana Desiatkina

Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland

T

Timo Felder

Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland

G

Ghalia Boubaker

Vetsuisse Faculty, Institute of Parasitology, University of Bern, Länggassstrasse 122, CH-3012 Bern, Switzerland

Y

Yosra Amdouni

Vetsuisse Faculty, Institute of Parasitology, University of Bern, Länggassstrasse 122, CH-3012 Bern, Switzerland; Laboratoire de Parasitologie, Institution de la Recherche et de l’Enseignement Supérieur Agricoles, École Nationale de Médecine Vétérinaire de Sidi Thabet, University of Manouba, Sidi Thabet 2020, Tunisia

J

Jessica Ramseier

Vetsuisse Faculty, Institute of Parasitology, University of Bern, Länggassstrasse 122, CH-3012 Bern, Switzerland

M

Martin Hungerbühler

Department of BioMedical Research, Experimental Radiology, University of Bern, CH-3008 Bern, Switzerland; Department of Diagnostic, Interventional and Pediatric Radiology, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland

C

Christoph Kempf

Department of BioMedical Research, Experimental Radiology, University of Bern, CH-3008 Bern, Switzerland; Department of Diagnostic, Interventional and Pediatric Radiology, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland

J

Johannes Thomas Heverhagen

Department of BioMedical Research, Experimental Radiology, University of Bern, CH-3008 Bern, Switzerland; Department of Diagnostic, Interventional and Pediatric Radiology, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland

A

Andrew Hemphill

Vetsuisse Faculty, Institute of Parasitology, University of Bern, Länggassstrasse 122, CH-3012 Bern, Switzerland

N

Nico Ruprecht

Department of BioMedical Research, Experimental Radiology, University of Bern, CH-3008 Bern, Switzerland; Department of Diagnostic, Interventional and Pediatric Radiology, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland

J

Julien Furrer

Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland

E

Emilia Păunescu

Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland

Cite This Article

Valentin Studer, Nicoleta Anghel, Oksana Desiatkina, et al. (2020). Conjugates Containing Two and Three Trithiolato-Bridged Dinuclear Ruthenium(II)-Arene Units as In Vitro Antiparasitic and Anticancer Agents. Pharmaceuticals, 13(12), 471. https://doi.org/10.3390/ph13120471

Conjugates Containing Two and Three Trithiolato-Bridged Dinuclear Ruthenium(II)-Arene Units as In Vitro Antiparasitic and Anticancer Agents

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