Coumarin‐Tagged Dinuclear Trithiolato‐Bridged Ruthenium(II)⋅Arene Complexes: Photophysical Properties and Antiparasitic Activity

• Published in: Chembiochem : a European journal of chemical biology Vol. 21; no. 19; pp. 2818 - 2835
• Main Authors: Desiatkina, Oksana, Păunescu, Emilia, Mösching, Martin, Anghel, Nicoleta, Boubaker, Ghalia, Amdouni, Yosra, Hemphill, Andrew, Furrer, Julien
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.10.2020; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Subjects: Antiparasitic agents; antiprotozoal agents; Biochemistry & Molecular Biology; Biological properties; Cell growth; Cell proliferation; Chemistry, Medicinal; Conjugates; Coumarin; cytotoxicity; Dyes; Fibroblasts; Fluorescence; Life Sciences & Biomedicine; Parasites; Pharmacology & Pharmacy; Protozoa; Pyrimethamine; Ruthenium; Ruthenium compounds; sandwich complexes; Science & Technology; Toxoplasma gondii; Transmission electron microscopy; OXIDATION; NEOSPORA-CANINUM; coumarin; ANTICANCER AGENTS; antiprotozoal agents; HALF-SANDWICH COMPLEXES; sandwich complexes; ruthenium; RHODAMINE 6G; IN-VITRO; 7-HYDROXYCOUMARIN; Toxoplasma gondii; RUTHENIUM COMPLEXES; CHEMISTRY; cytotoxicity
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.202000174

The synthesis, characterization, photophysical and biological properties of 13 new conjugate coumarin‐diruthenium(II)⋅arene complexes against Toxoplasma gondii are presented. For all conjugate organometallic unit/coumarins, an almost complete loss of fluorescence efficacy was observed. However, the nature of the fluorophore, the type of bonding, the presence and length of a linker between the coumarin dye and the ruthenium(II) moiety, and the number of dye units influenced their biological properties. The in vitro activity against a transgenic T. gondii strain grown in human foreskin fibroblasts (HFF) leads to IC50 values for T. gondii β‐gal from 105 to 735 nM. Of note is that nine compounds displayed lower IC50 than the standard drug pyrimethamine. One compound applied at its IC50 did not affect B‐cell proliferation but had an impact on T‐cell proliferation in murine splenocyte cultures. Transmission electron microscopy of T. gondii β‐gal‐infected HFF showed that treatment predominantly affected the parasites’ mitochondrion. The (para)site for treatment: Thirteen coumarin‐diruthenium(II)⋅arene conjugates were evaluated against a transgenic T. gondii strain grown in human foreskin fibroblasts (HFF). The IC50 values ranged from 105 to 735 nM, with nine compounds displaying a lower IC50 than the standard drug pyrimethamine. TEM of T. gondii‐infected HFF showed that treatment predominantly affected the parasites’ mitochondrion.