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dc.contributor.authorLe, Thuy G
dc.contributor.authorKundu, Abhijit
dc.contributor.authorGhoshal, Atanu
dc.contributor.authorNguyen, Nghi H
dc.contributor.authorPreston, Sarah
dc.contributor.authorJiao, Yaqing
dc.contributor.authorRuan, Banfeng
dc.contributor.authorXue, Lian
dc.contributor.authorHuang, Fei
dc.contributor.authorKeiser, Jennifer
dc.contributor.authorHofmann, Andreas
dc.contributor.authorChang, Bill CH
dc.contributor.authorGarcia-Bustos, Jose
dc.contributor.authorWells, Timothy NC
dc.contributor.authorPalmer, Michael J
dc.contributor.authorJabbar, Abdul
dc.contributor.authorGasser, Robin B
dc.contributor.authorBaell, Jonathan B
dc.date.accessioned2019-07-04T12:33:20Z
dc.date.available2019-07-04T12:33:20Z
dc.date.issued2019
dc.identifier.issn0022-2623
dc.identifier.doi10.1021/acs.jmedchem.8b01789
dc.identifier.urihttp://hdl.handle.net/10072/382751
dc.description.abstractRecently, we have discovered that the registered pesticide, tolfenpyrad, unexpectedly and potently inhibits the development of the L4 larval stage of the parasitic nematode Haemonchus contortus with an IC50 value of 0.03 μM while displaying good selectivity, with an IC50 of 37.9 μM for cytotoxicity. As a promising molecular template for medicinal chemistry optimization, we undertook anthelmintic structure–activity relationships for this chemical. Modifications of the left-hand side (LHS), right-hand side (RHS), and middle section of the scaffold were explored to produce a set of 57 analogues. Analogues 25, 29, and 33 were shown to be the most potent compounds of the series, with IC50 values at a subnanomolar level of potency against the chemotherapeutically relevant fourth larval (L4) stage of H. contortus. Selected compounds from the series also showed promising activity against a panel of other different parasitic nematodes, such as hookworms and whipworms.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAMER CHEMICAL SOC
dc.relation.ispartofpagefrom1036
dc.relation.ispartofpageto1053
dc.relation.ispartofissue2
dc.relation.ispartofjournalJOURNAL OF MEDICINAL CHEMISTRY
dc.relation.ispartofvolume62
dc.subject.fieldofresearchMedicinal and biomolecular chemistry
dc.subject.fieldofresearchOrganic chemistry
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3404
dc.subject.fieldofresearchcode3405
dc.subject.fieldofresearchcode3214
dc.titleStructure-Activity Relationship Studies of Tolfenpyrad Reveal Subnanomolar Inhibitors of Haemonchus contortus Development
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2019 This document is the post-print of a Published Work that appeared in final form in the Journal of Medicinal Chemistry, copyright 2019 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see 10.1021/acs.jmedchem.8b01789
gro.hasfulltextFull Text
gro.griffith.authorHofmann, Andreas


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