Analogues of 1,5-bis(4-amidinophenoxy)pentane (pentamidine) in the treatment of experimental Pneumocystis carinii pneumonia
| Autor: | M. Cory, Susan Jones, J. D. Geratz, J. E. Hall, R R Tidwell, Kwasi A. Ohemeng |
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| Rok vydání: | 1990 |
| Předmět: |
Drug
Male Chemical Phenomena media_common.quotation_subject Amidines Thymidylate synthase Microbiology Structure-Activity Relationship Pharmacokinetics Anti-Infective Agents Drug Discovery medicine Animals Pentamidine media_common biology Chemistry Pneumonia Pneumocystis Biological activity Rats Inbred Strains DNA Thymidylate Synthase respiratory tract diseases Benzamidines Rats Pneumocystis carinii Enzyme inhibitor Toxicity biology.protein Molecular Medicine Trypsin Inhibitors medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 33(4) |
| ISSN: | 0022-2623 |
| Popis: | A series of 33 analogues of the anti-Pneumocystis carinii drug 1,5-bis(4-amidinophenoxy)pentane (pentamidine) was synthesized for screening against a rat model of P. carinii pneumonia (PCP). Twenty-five of the compounds showed efficacy against PCP when compared to a saline-treated control group. Two compounds, 1,4-bis(4-amidinophenoxy)butane (butamidine, 6) and 1,3-bis(4-amidino-2-methoxyphenoxy)propane (DAMP, 16), were statistically more effective than the parent drug in treating PCP in the rat model of infection. In addition to their activity against PCP, the compounds were also evaluated for antitrypsin activity, ability to inhibit thymidylate synthetase, affinity for DNA, and toxicity. No correlation was observed between the tested molecular interactions of the diamidines and their effectiveness against PCP. |
| Databáze: | OpenAIRE |
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