2019
DOI: 10.1016/j.ijpddr.2018.12.007
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Tetrahydroquinoxalines induce a lethal evisceration phenotype in Haemonchus contortus in vitro

Abstract: In the present study, the anthelmintic activity of a human tyrosine kinase inhibitor, AG-1295, and 14 related tetrahydroquinoxaline analogues against Haemonchus contortus was explored. These compounds were screened against parasitic larvae - exsheathed third-stage (xL3) and fourth-stage (L4) - using a whole-organism screening assay. All compounds were shown to have inhibitory effects on larval motility, development and growth, and induced evisceration through the excretory pore in xL3s. The estimated IC50 valu… Show more

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Cited by 16 publications
(14 citation statements)
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“…The phenotypic changes recorded by video in xL3s after 7 days were examined further by light microscopy. A detailed examination of BLK127-treated xL3s revealed an ‘eviscerated’ (Evi) phenotype, consistent with that described by Jiao et al [20].…”
Section: Resultssupporting
confidence: 88%
See 1 more Smart Citation
“…The phenotypic changes recorded by video in xL3s after 7 days were examined further by light microscopy. A detailed examination of BLK127-treated xL3s revealed an ‘eviscerated’ (Evi) phenotype, consistent with that described by Jiao et al [20].…”
Section: Resultssupporting
confidence: 88%
“…The first compound, BLK127, induced an Evi phenotype, which is likely linked to an adverse effect of this compound on the excretory/secretory system (cf. [20]). The excretory pore is assumed to have an osmoregulatory function as well as a role in exsheathment [21].…”
Section: Discussionmentioning
confidence: 99%
“…2), but not with GNT, even at 500 μM, the concentration at which the compound inhibited L4 development by 100%. This phenotype has been described previously as an initial anterior protrusion followed by evisceration (Evi) (Jiao et al, 2018). For both DMY and YGN, the lowest concentration to induce the Evi phenotype was 12.5 μM (at 7 days), while it was 50 μM for compound DHK (Fig.…”
Section: Resultsmentioning
confidence: 77%
“…The potency of compound 4 to inhibit the motility of L4 was greater than its effect on xL3, which might be explained by the well-developed mouth and pharynx in the L4 stage, resulting in more rapid oral uptake into and accumulation of the compound in the worm (cf. [42,43]). The Sks-phenotype in L4s and the substantial subcuticular tissue destruction in the adult stage of H. contortus bode well for further work on this and similar chemical scaffolds.…”
Section: Discussionmentioning
confidence: 99%