Tirandamycins from Streptomyces sp. 17944 inhibiting the parasite Brugia malayi asparagine tRNA synthetase

Org Lett. 2011 Apr 15;13(8):2034-7. doi: 10.1021/ol200420u. Epub 2011 Mar 15.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aminoglycosides / chemistry*
  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Aspartate-tRNA Ligase / antagonists & inhibitors*
  • Brugia malayi / drug effects*
  • Brugia malayi / enzymology
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Models, Molecular
  • Molecular Structure
  • RNA, Transfer, Amino Acyl / antagonists & inhibitors*
  • Streptomyces / chemistry*

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • RNA, Transfer, Amino Acyl
  • Aspartate-tRNA Ligase
  • asparaginyl-tRNA synthetase