A New Class of Antituberculosis Agents
| Autor: | Craig A. Townsend, Nikki M. Parrish, Todd Ashley Houston, Niharika P. Bansal, Anthony Stapon, Paul B. Jones, James D. Dick |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
biology
Stereochemistry medicine.drug_class Antitubercular Agents Carboxamide Biological activity Microbial Sensitivity Tests Mycobacterium tuberculosis biology.organism_classification Amides Chemical synthesis Sulfone Structure-Activity Relationship chemistry.chemical_compound chemistry Biochemistry Drug Discovery medicine Molecular Medicine Structure–activity relationship Sulfones Fatty acid synthesis Antibacterial agent |
| Zdroj: | Journal of Medicinal Chemistry. 43:3304-3314 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Long-chain lipid envelopes are characteristic of mycobacteria such as those that cause tuberculosis and leprosy. Inhibition of fatty acid synthesis or elongation is a strategy demonstrated to be clinically effective against M. tuberculosis. A new class of compounds designed to inhibit the beta-ketoacyl synthase reaction of fatty acid synthesis has been developed. Of >30 compounds described, the most active were acetamides containing alkylsulfonyl substituents. Inhibitory activities were acutely sensitive to net charge, chain length, and degree of unsaturation. The most active compound 5 (alkyl = C(10)) contained a single methylene spacer between the sulfone and carboxamide and exhibited an MIC of 0.75-1.5 microg/mL, comparable to first-line antituberculosis drugs. These compounds are species-specific, exhibiting no significant activity against bacterial species other than M. tuberculosis and closely related strains. The synthesis, biological activity, and specificity of these compounds are described. |
| Databáze: | OpenAIRE |
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