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

Abstract

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 BODIPYtrithiolato-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.

New Nucleic Base-Tethered Trithiolato-Bridged Dinuclear Ruthenium(II)-Arene Compounds: Synthesis and Antiparasitic Activity

“…Noteworthy, TEM (transmission electron microscopy) studies of different protozoan parasites ( Toxoplasma gondii , Neospora caninum , Trypanosoma brucei ) treated with trithiolato dinuclear ruthenium(II)-arene complexes revealed alterations in the mitochondrial ultrastructure pointing out this organelle as a potential target [ 89 ]. Interestingly, a similar effect was also observed in the case of trithiolato diruthenium conjugates with coumarin and BODIPY fluorophores [ 93 , 94 ].…”

“…Compounds 7 , 14 , and 30 have an ester linker that can potentially be hydrolyzed in growth media. Comparable conjugates with coumarin and BODIPY fluorescent units linked through ester bonds to the diruthenium unit were recently investigated [ 93 , 94 ]. As a very limited solvolysis of the ester bonds was noticed after 168 h for some compounds, it was concluded that the coumarin and BODIPY diruthenium conjugates exhibit high stability in the conditions used for the biological evaluations [ 93 ].…”

“…The straightforward synthesis and scale-up of mixed trithiolato dinuclear ruthenium complexes like complex O ( Figure 1 ) as well as their outstanding chemical inertness make this scaffold a good substrate for functionalization. Diruthenium conjugates with short peptides [ 92 ], coumarins [ 93 ], BODIPYs [ 94 ], and anticancer and antimicrobial drugs [ 95 , 96 ] have been reported and some of them exhibited improved water solubility, as well as enhanced anticancer or antiparasitic activity.…”

Trithiolato-Bridged Dinuclear Arene Ruthenium(ll)- Glycoconjugates: Synthesis and Antiparasitic Activity

“…The synthesis of the trithiolato diruthenium complexes is generally straightforward and efficient [90][91][92], and this scaffold is robust to chemical modification and easily adaptable to the conjugate strategy as demonstrated by the various series of hybrids with peptides [93], drugs [94,95], fluorophores [92] , [96] or metabolites [97]. Ester and amide couplings [92,98], but also CuAAC (Cu(I)catalyzed azide-alkyne cycloaddition) click reactions [95] , [97] proved to be useful tools for the functionalization of the diruthenium trithiolato unit at the level of the bridge thiols.…”

“…For determination of IC50 on T. gondii β-gal, eight serial concentrations ranging from 7 nM to 1 μM were tested for each selected compound as previously described [92,95,96].…”