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.
![]()
|
PDF
- Accepted Version
611Kb |
Official URL: http://edoc.unibas.ch/dok/A5843029
Downloads: Statistics Overview
Abstract
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 |
ISSN: | 0022-2623 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Language: | English |
Related URLs: | |
Identification Number: |
|
edoc DOI: | |
Last Modified: | 20 Oct 2017 12:01 |
Deposited On: | 14 Sep 2012 06:52 |
Repository Staff Only: item control page