by Akama T, Freund YR, Berry PW, Carter DS, Easom EE, Jarnagin K, Lunde CS, Plattner JJ, Rock F, Stefanakis R, Fischer C, Bulman CA, Lim KC, Suzuki BM, Tricoche N, Mansour A, DiCosty U, McCall S, Carson B, McCall JW, McKerrow J, Hübner MP, Specht S, Hoerauf A, Lustigman S, Sakanari JA, Jacobs RT. ACS Infectious Diseases 2020;6(2)173-179. doi: 10.1021/acsinfecdis.9b00396
Summary: Flubendazole has been shown to kill adult filarial worms, providing promise that this molecule could be useful in the treatment of onchocerciasis and lymphatic filariasis, however, it suffers from several limitations. The authors prepared a series of benzimidazole–benzoxaborole analogues in an attempt to overcome these. These exhibited good in vitro activity against Onchocerca volvulus, the nematode responsible for onchocerciasis. In vivo results suggested that these benzimidazole drugs require a long (>28 day) exposure to the drug to be effective. Although the authors were encouraged by the proof of concept, it was clear that the lead molecule from the series would not meet the target candidate profile. An additional series of hybrid molecules is being explored.