| Autor: |
Jones, P. B., Parrish, N. M., Houston, T. A., Stapon, A., Bansal, N. P., Dick, J. D., Townsend, C. A. |
| Zdroj: |
Journal of Medicinal Chemistry; August 24, 2000, Vol. 43 Issue: 17 p3304-3314, 11p |
| Abstrakt: |
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 β-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 = C10) contained a single methylene spacer between the sulfone and carboxamide and exhibited an MIC of 0.75−1.5 μg/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: |
Supplemental Index |
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