Synthesis, Photophysical Properties and Biological Evaluation of New Conjugates BODIPY: Dinuclear Trithiolato‐Bridged Ruthenium(II)‐Arene Complexes

• Published in: Chembiochem : a European journal of chemical biology Vol. 23; no. 23; pp. e202200536 - n/a
• Main Authors: Desiatkina, Oksana, Boubaker, Ghalia, Anghel, Nicoleta, Amdouni, Yosra, Hemphill, Andrew, Furrer, Julien, Păunescu, Emilia
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 05.12.2022; Wiley Subscription Services, Inc
• Subjects: antiparasitic activity; Antiparasitic agents; Antiparasitic Agents - chemistry; Antiparasitic Agents - pharmacology; antiprotozoal agents; Biochemistry & Molecular Biology; Biological activity; Biological properties; BODIPY; Boron Compounds - chemistry; Chemistry, Medicinal; Conjugates; Evaluation; Fluorescence; Fluorescent Dyes - chemistry; Fluorescent indicators; Humans; Hybrids; Life Sciences & Biomedicine; Pharmacology & Pharmacy; photophysical properties; Ruthenium; Ruthenium - chemistry; Ruthenium compounds; Science & Technology; Synthesis; Tachyzoites; Toxoplasma gondii; POLYPYRIDINE COMPLEXES; HOST-CELLS; BODIPY; photophysical properties; NEOSPORA-CANINUM; antiprotozoal agents; TOXOPLASMA; antiparasitic activity; ANTICANCER ACTIVITY; IN-VITRO; Toxoplasma gondii; fluorescence; ARENE RUTHENIUM COMPLEXES; METAL-BASED DRUGS; CELLULAR-LOCALIZATION; DERIVATIVES
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.202200536

The synthesis, photophysical properties and antiparasitic efficacy against Toxoplasma gondii β‐gal (RH strain tachyzoites expressing β‐galactosidase) grown in human foreskin fibroblast monolayers (HFF) of a series of 15 new conjugates BODIPY‐trithiolato‐bridged dinuclear ruthenium(II)‐arene complexes are reported (BODIPY=4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene, derivatives used as fluorescent markers). The influence of the bond type (amide vs. ester), as well as that of the length and nature (alkyl vs. aryl) of the spacer between the dye and the diruthenium(II) complex moiety, on fluorescence and biological activity were evaluated. The assessed photophysical properties revealed that despite an important fluorescence quenching effect observed after conjugating the BODIPY to the diruthenium unit, the hybrids could nevertheless be used as fluorescent tracers. Although the antiparasitic activity of this series of conjugates appears limited, the compounds demonstrate potential as fluorescent probes for investigating the intracellular trafficking of trithiolato‐bridged dinuclear Ru(II)‐arene complexes in vitro. Fifteen new dinuclear arene‐ruthenium (II)‐BODIPY conjugates were synthesized. Despite a fluorescence quenching effect, these conjugates can be used as fluorescent tracers. Their antiparasitic activity but also their toxicity against healthy human foreskin fibroblasts (HFFs) was reduced compared to the parent ruthenium compounds. TEM images revealed profound alterations of the tachyzoite mitochondrion.