Abstract
Lymphatic filariasis is caused by the parasitic nematodes Brugia malayi and Wuchereria bancrofti, and asparaginyl-tRNA synthetase (AsnRS) is considered an excellent antifilarial target. The discovery of three new tirandamycins (TAMs), TAM E (1), F (2), and G (3), along with TAM A (4) and B (5), from Streptomyces sp. 17944 was reported. Remarkably, 5 selectively inhibits the B. malayi AsnRS and efficiently kills the adult B. malayi parasite, representing a new lead scaffold to discover and develop antifilarial drugs.
© 2011 American Chemical Society
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Aminoglycosides / chemistry*
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Animals
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Anti-Bacterial Agents / chemistry*
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Aspartate-tRNA Ligase / antagonists & inhibitors*
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Brugia malayi / drug effects*
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Brugia malayi / enzymology
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Models, Molecular
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Molecular Structure
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RNA, Transfer, Amino Acyl / antagonists & inhibitors*
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Streptomyces / chemistry*
Substances
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Aminoglycosides
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Anti-Bacterial Agents
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Enzyme Inhibitors
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RNA, Transfer, Amino Acyl
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Aspartate-tRNA Ligase
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asparaginyl-tRNA synthetase