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Organometallic Derivatives of Decoquinate Targeted toward Toxoplasma gondii


Betts, Harley D; Ong, Yih Ching; Anghel, Nicoleta; Keller, Sarah; Karges, Johannes; Voutsara, Niovi; Müller, Joachim; Manoury, Eric; Blacque, Olivier; Cariou, Kevin; Hemphill, Andrew; Gasser, Gilles (2022). Organometallic Derivatives of Decoquinate Targeted toward Toxoplasma gondii. Organometallics, 41(15):2035-2041.

Abstract

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

Abstract

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

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Physical Sciences > Physical and Theoretical Chemistry
Physical Sciences > Organic Chemistry
Physical Sciences > Inorganic Chemistry
Uncontrolled Keywords:Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry
Language:English
Date:8 August 2022
Deposited On:09 Nov 2022 13:52
Last Modified:27 Apr 2024 01:41
Publisher:American Chemical Society (ACS)
ISSN:0276-7333
OA Status:Green
Publisher DOI:https://doi.org/10.1021/acs.organomet.2c00204
Project Information:
  • : FunderSNSF
  • : Grant ID310030_184662
  • : Project TitleEffects of a double-edged sword: exploiting the interaction between immunity and chemotherapy in murine and ovine models of congenital neosporosis and toxoplasmosis
  • : FunderSNSF
  • : Grant IDCRSII5_173718
  • : Project TitleRuthenium Complexes for the Treatment of Protozoan Diseases of Medical and Veterinary Importance
  • : FunderAlexander von Humboldt-Stiftung
  • : Grant ID
  • : Project Title
  • Content: Accepted Version