title: Tirandamycins from Streptomyces sp. 17944 inhibiting the parasite Brugia malayi asparagine tRNA synthetase.
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.
authors.affiliation: Department of Chemistry, Scripps Florida, Jupiter, Florida 33458, USA.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Yu
authors.forename: Sanja
authors.initials: S
authors.lastname: Vodanovic-Jankovic
authors.forename: Nathan
authors.initials: N
authors.lastname: Ledeboer
authors.forename: Sheng-Xiong
authors.initials: SX
authors.lastname: Huang
authors.forename: Scott R
authors.initials: SR
authors.lastname: Rajski
authors.forename: Michael
authors.initials: M
authors.lastname: Kron
authors.forename: Ben
authors.initials: B
authors.lastname: Shen
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001226:Aspartate-tRNA Ligase / Q000037:antagonists & inhibitors*; D017178:Brugia malayi / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D012346:RNA, Transfer, Amino Acyl / Q000037:antagonists & inhibitors*; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D012346:RNA, Transfer, Amino Acyl; D001226:Aspartate-tRNA Ligase; C029194:asparaginyl-tRNA synthetase