Lymphatic filariasis is caused by the Brugia malayiparasite. Three new congeners of the depsipeptide WS9326A (1), WS9326C (2), WS9326D (3), and WS9326E (4), were isolated from Streptomycessp. 9078 by using a B. malayiasparaginyl-tRNA synthetase (BmAsnRS) inhibition assay. WS9326D specifically inhibits the BmAsnRS, kills the adult B. malayiparasite, and does not exhibit significant general cytotoxicity to human hepatic cells, representing a new lead scaffold for antifilarial drug discovery. [ABSTRACT FROM AUTHOR]