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In vitro metabolic profile and in vivo antischistosomal activity studies of (η(6)-praziquantel)Cr(CO)3 derivatives

Patra, Malay and Ingram, Katrin and Leonidova, Anna and Pierroz, Vanessa and Ferrari, Stefano and Robertson, Murray N. and Todd, Matthew H. and Keiser, Jennifer and Gasser, Gilles. (2013) In vitro metabolic profile and in vivo antischistosomal activity studies of (η(6)-praziquantel)Cr(CO)3 derivatives. Journal of medicinal chemistry, 56 (22). pp. 9192-9198.

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Official URL: http://edoc.unibas.ch/dok/A6212250

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Abstract

In vitro metabolic behavior was investigated for two chromium tricarbonyl derivatives of the antischistosomal drug praziquantel (PZQ) with the formula (η(6)-PZQ)Cr(CO)3 (1 and 2), by use of human liver microsomes. The metabolic profiles of the derivatives differ significantly. The optically pure (η(6)-PZQ)Cr(CO)3 derivatives (S, Sp)-1, (R, Rp)-1, (S, Rp)-2, and (R, Sp)-2 were also prepared to assess the eudysmic ratios of 1 and 2 against Schistosoma mansoni in vitro. A strong enantioselective antischistosomal activity was observed. The R-enantiomers are highly active against adult schistosomes in vitro (IC50 0.08-0.13 μM), whereas both S-enantiomers lack activity. The in vivo activity of 1 and 2 was then studied in mice harboring a chronic S. mansoni infection. A single dose of 1 and 2 (400 mg/kg) resulted in low worm burden reductions of 24% and 29% (p < 0.05).
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Helminth Drug Development (Keiser)
UniBasel Contributors:Keiser, Jennifer
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Chemical Society
ISSN:0022-2623
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:20 Oct 2017 11:06
Deposited On:27 Mar 2014 13:13

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