{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:16:11Z","timestamp":1788304571961,"version":"build-2803163510"},"reference-count":35,"publisher":"American Chemical Society (ACS)","issue":"13","license":[{"start":{"date-parts":[[2015,6,11]],"date-time":"2015-06-11T00:00:00Z","timestamp":1433980800000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The L3-stage-specific chitinase OvCHT1 has been implicated in the development of Onchocerca volvulus, the causative agent of onchocerciasis. Closantel, a known anthelmintic drug, was previously discovered as a potent and specific OvCHT1 inhibitor. As closantel is also a known protonophore, we performed a simple scaffold modulation to map out the structural features that are relevant for its individual or dual biochemical roles. Furthermore, we present that either OvCHT1 inhibition or protonophoric activity was capable of affecting O. volvulus L3 molting and that the presence of both activities in a single molecule yielded more potent inhibition of the nematode\u2019s developmental process.<\/jats:p>","DOI":"10.1021\/jm5006435","type":"journal-article","created":{"date-parts":[[2014,6,11]],"date-time":"2014-06-11T11:12:30Z","timestamp":1402485150000},"page":"5792-5799","source":"Crossref","is-referenced-by-count":32,"title":["Dual Protonophore\u2013Chitinase\nInhibitors Dramatically\nAffect\n                    <i>O. volvulus<\/i>\n                    Molting"],"prefix":"10.1021","volume":"57","author":[{"given":"Major","family":"Gooyit","sequence":"first","affiliation":[{"name":"The Skaggs Institute for Chemical Biology, and The Worm Institute of Research and Medicine, The Scripps Research Institute , , 10550 North Torrey Pines Road , , ,","place":["La Jolla, California, United States, 92037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Tricoche","sequence":"additional","affiliation":[{"name":"New York Blood Center , , , ,","place":["New York, New York, United States, 10065"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lustigman","sequence":"additional","affiliation":[{"name":"New York Blood Center , , , ,","place":["New York, New York, United States, 10065"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim D.","family":"Janda","sequence":"additional","affiliation":[{"name":"The Skaggs Institute for Chemical Biology, and The Worm Institute of Research and Medicine, The Scripps Research Institute , , 10550 North Torrey Pines Road , , ,","place":["La Jolla, California, United States, 92037"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,6,11]]},"reference":[{"key":"2026090118413193000_cit1","doi-asserted-by":"crossref","first-page":"e217","DOI":"10.1371\/journal.pntd.0000217","article-title":"Of mice, cattle, and humans: the\nimmunology and treatment of river blindness","volume":"2","author":"Allen","year":"2008","journal-title":"PLoS Negl. Trop. Dis."},{"key":"2026090118413193000_cit2","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1038\/nrmicro1048","article-title":"The life and times\nof ivermectin\u2500a success story","volume":"2","author":"Omura","year":"2004","journal-title":"Nature\nRev. Microbiol."},{"key":"2026090118413193000_cit3","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1179\/000349804225003442","article-title":"Thirty-month follow-up of sub-optimal responders to\nmultiple treatments with ivermectin, in two onchocerciasis-endemic\nfoci in Ghana","volume":"98","author":"Awadzi","year":"2004","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"2026090118413193000_cit4","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/S1473-3099(08)70099-9","article-title":"Effect of\nsingle-dose ivermectin on Onchocerca volvulus: a systematic review and meta-analysis","volume":"8","author":"Basanez","year":"2008","journal-title":"Lancet\nInfect. 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Res."},{"key":"2026090118413193000_cit8","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1074\/jbc.271.3.1441","article-title":"Identification of chitinase\nas the\nimmunodominant filarial antigen recognized by sera of vaccinated rodents","volume":"271","author":"Adam","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2026090118413193000_cit9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/0166-6851(93)90054-2","article-title":"Chitinolytic activities\nin Heligmosomoides polygyrus and their\nrole in egg hatching","volume":"58","author":"Arnold","year":"1993","journal-title":"Mol. Biochem. Parasitol."},{"key":"2026090118413193000_cit10","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1128\/IAI.00701-07","article-title":"Essential role of chitinase\nin the development of the filarial nematode Acanthocheilonema viteae","volume":"76","author":"Tachu","year":"2008","journal-title":"Infect. Immun."},{"key":"2026090118413193000_cit11","doi-asserted-by":"crossref","first-page":"42557","DOI":"10.1074\/jbc.M103479200","article-title":"Expression\nand secretion of a larval-specific chitinase (family 18 glycosyl hydrolase)\nby the infective stages of the parasitic nematode Onchocerca volvulus","volume":"276","author":"Wu","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2026090118413193000_cit12","doi-asserted-by":"crossref","first-page":"3424","DOI":"10.1073\/pnas.0915125107","article-title":"Repositioning\nof an existing drug for the neglected tropical disease Onchocerciasis","volume":"107","author":"Gloeckner","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026090118413193000_cit13","first-page":"851","article-title":"Closantel, a new antiparasitic hydrogen\nionophore [proceedings]","volume":"87","author":"Van Den Bossche","year":"1979","journal-title":"Arch. Int. 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