Organometallic Derivatives of Decoquinate Targeted toward Toxoplasma gondii

Harley D Betts (1) , Yih Ching Ong (1) , Nicoleta Anghel , Sarah Keller (1) , Johannes Karges (1) , Niovi Voutsara (1) , Joachim Müller , Eric Manoury (2) , Olivier Blacque , Kevin Cariou (1) , Andrew Hemphill , Gilles Gasser (1)

1 ENSCP - Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL
2 LCC - Laboratoire de chimie de coordination

Toxoplasmosis is an infection contracted by exposure to Toxoplasma gondii and can have deleterious health effects on pregnant women and their children. Current treatments for the infection are complex and have considerable undesired side effects, raising the need for new treatments. Herein, we report the synthesis, characterization, and biological testing of some organometallic derivatives of the commercially available, broad-spectrum antiparasitic, decoquinate (DCQ). The cyclic secondary amine of decoquinate was functionalized with a range of groups (i.e., ferrocene, ruthenocene, and phenyl) with either methyl or vinyl bridges. Through measurement of half maximal inhibitory concentrations (IC50) and T. gondii proliferation assays, it was found that ferrocenylvinyl-DCQ and an oxygen-alkylated phenylvinyl-DCQ side product reduced proliferation of the parasite by 84% at 1 μM, which approached that of the parent drug (96%). These data provide a possible roadmap for future investigations on the derivatization of DCQ to yield better treatments for toxoplasmosis, particularly the functionalization of the cyclic ketone.

Mots clés: Bioorganometallic Chemistry; Ferrocene; Medicinal Organometallic Chemistry; Toxoplasma gondii; Toxoplasmosis

Domaines: Chimie thérapeutique

Harley D Betts, Yih Ching Ong, Nicoleta Anghel, Sarah Keller, Johannes Karges, et al.. Organometallic Derivatives of Decoquinate Targeted toward Toxoplasma gondii. Organometallics, 2022, ⟨10.1021/acs.organomet.2c00204⟩. ⟨hal-03727450⟩