Arylpyrrole and fipronil analogues that inhibit the motility and/or development of Haemonchus contortus in vitro

Publication date: Available online 4 June 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): H.M.P. Dilrukshi Herath, Hongjian Song, Sarah Preston, Abdul Jabbar, Tao Wang, Sean L. McGee, Andreas Hofmann, Jose Garcia-Bustos, Bill C.H. Chang, Anson V. Koehler, Yuxiu Liu, Qiaoqiao Ma, Pengxiang Zhang, Qiqi Zhao, Qingmin Wang, Robin B. GasserAbstractDue to widespread drug resistance in parasitic nematodes, there is a need develop new anthelmintics. Given the cost and time involved in developing a new drug, the repurposing of known chemicals can be a promising, alternative approach. In this context, we tested a library (n = 600) of natural product-inspired pesticide analogues against exsheathed third stage-larvae (xL3s) of Haemonchus contortus (barber's pole worm) using a whole-organism, phenotypic screening technique that measures the inhibition of motility and development in treated larvae. In the primary screen, we identified 32 active analogues derived from chemical scaffolds of arylpyrrole or fipronil. The seven most promising compounds, selected based on their anthelmintic activity and/or limited cytotoxicity, are arylpyrroles that reduced the motility of fourth-stage larvae (L4s) with significant potency (IC50 values ranged from 0.04 ± 0.01 μM to 4.25 ± 0.82 μM, and selectivity indices ranged from 10.6 to 412.5). Since the parent structures of the active compounds are uncouplers of oxidative phosphorylation, we tested...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research