Structure-activity studies of dicationically substituted bis-benzimidazoles against Giardia lamblia: correlation of antigiardial activity with DNA binding affinity and giardial topoisomerase II inhibition
| Autor: | C. A. Bell, Christine C. Dykstra, Richard R. Tidwell, N A Naiman, M. Cory, T. A. Fairley |
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| Rok vydání: | 1993 |
| Předmět: |
Protozoan Proteins
Structure-Activity Relationship chemistry.chemical_compound Cations Animals Topoisomerase II Inhibitors Structure–activity relationship Pharmacology (medical) Pharmacology chemistry.chemical_classification biology Topoisomerase Biological activity DNA Protozoan Molecular biology In vitro DNA Topoisomerases Type II Infectious Diseases Enzyme chemistry Biochemistry Enzyme inhibitor biology.protein Benzimidazoles Giardia lamblia Topoisomerase-II Inhibitor DNA Research Article |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 37:2668-2673 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.37.12.2668 |
| Popis: | Nine dicationically substituted bis-benzimidazoles were examined for their in vitro activities against Giardia lamblia WB (ATCC 30957). The potential mechanisms of action of these compounds were evaluated by investigating the relationship among in vitro antigiardial activity and the affinity of the molecules for DNA and their ability to inhibit the activity of giardial topoisomerase II. Each compound demonstrated antigiardial activity, as measured by assessing the incorporation of [methyl-3H]thymidine by giardial trophozoites exposed to the test agents. Three compounds exhibited excellent in vitro antigiardial activities, with 50% inhibitory concentrations which compared very favorably with those of two currently used drugs, quinacrine HCl and metronidazole. Putative mechanisms of action for these compounds were suggested by the strong correlation observed among in vitro antigiardial activity and the affinity of the molecules for natural and synthetic DNA and their ability to inhibit the relaxation activity of giardial topoisomerase II. A strong correlation between the DNA binding affinity of these compounds and their inhibition of giardial topoisomerase II activity was also observed. |
| Databáze: | OpenAIRE |
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