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

Studer, Valentin; Anghel, Nicoleta; Desiatkina, Oksana; Felder, Timo; Boubaker, Ghalia; Amdouni, Yosra; Ramseier, Jessica; Hungerbühler, Martin; Kempf, Christoph; Heverhagen, Johannes Thomas; Hemphill, Andrew; Ruprecht, Nico; Furrer, Julien; Păunescu, Emilia (2020). Conjugates Containing Two and Three Trithiolato-Bridged Dinuclear Ruthenium(II)-Arene Units as In Vitro Antiparasitic and Anticancer Agents. Pharmaceuticals, 13(12), p. 471. MDPI 10.3390/ph13120471

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic, Interventional and Paediatric Radiology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
08 Faculty of Science > Departement of Chemistry and Biochemistry
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Radiologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Radiologie

UniBE Contributor:

Studer, Valentin; Anghel, Nicoleta; Desiatkina, Oksana; Felder, Timo Markus Oskar; Boubaker, Ghalia; Amdouni, Yosra; Ramseier, Jessica; Hungerbuehler, Martin; Kempf, Christoph; Heverhagen, Johannes; Hemphill, Andrew; Ruprecht, Nico and Furrer, Julien

Subjects:

600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture
500 Science > 540 Chemistry
500 Science > 570 Life sciences; biology

ISSN:

1424-8247

Publisher:

MDPI

Language:

English

Submitter:

Julien Henri Lucien Furrer

Date Deposited:

21 Dec 2020 12:04

Last Modified:

21 Dec 2020 12:04

Publisher DOI:

10.3390/ph13120471

BORIS DOI:

10.7892/boris.149867

URI:

https://boris.unibe.ch/id/eprint/149867

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