Structure-activity relationship of an ozonide carboxylic acid (OZ78) against Fasciola hepatica

Zhao, Qingjie and Vargas, Mireille and Dong, Yuxiang and Zhou, Lin and Wang, Xiaofang and Sriraghavan, Kamaraj and Keiser, Jennifer and Vennerstrom, Jonathan L.. (2010) Structure-activity relationship of an ozonide carboxylic acid (OZ78) against Fasciola hepatica. Journal of medicinal chemistry, 53 (10). pp. 4223-4233.

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Official URL: http://edoc.unibas.ch/dok/A5843029

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In this paper, we describe the SAR of ozonide carboxylic acid OZ78 (1) as the first part of our search for a trematocidal synthetic peroxide drug development candidate. We found that relatively small structural changes to 1 resulted most commonly in loss of activity against Fasciola hepatica in vivo. A spiroadamantane substructure and acidic functional group (or ester prodrug) were required for activity. Of 26 new compounds administered at single 100 mg/kg oral doses to F. hepatica infected rats, 8 had statistically significant worm burden reductions, 7 were partially curative, and 1 (acylsulfonamide 6) was completely curative and comparable to 1 in flukicidal efficacy. This study also showed that the activity of 1 is peroxide-bond-dependent, suggesting that its flukicidal efficacy depends upon hemoglobin digestion in F. hepatica
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Helminth Drug Development (Keiser)
UniBasel Contributors:Keiser, Jennifer
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Oct 2017 12:01
Deposited On:14 Sep 2012 06:52

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