{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:13:35Z","timestamp":1790817215378,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T00:00:00Z","timestamp":1580688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The neglected tropical disease, schistosomiasis, is caused by trematode blood flukes of the Schistosoma genus and infects approximately 200 million people worldwide. With just one partially effective drug available for disease treatment, new drugs are urgently needed. Herein, a series of 47 phthalimide (Pht) analogues possessing high-value bioactive scaffolds (i.e., benzimidazole and 1,2,3,-triazoles) was synthesized by click-chemistry. Compounds were evaluated for anti-schistosomal activity in culture against somules (post-infective larvae) and adults of Schistosoma mansoni, their predicted ADME (absorption, distribution, metabolism, and excretion) properties, and toxicity vs. HepG2 cells. The majority showed favorable parameters for surface area, lipophilicity, bioavailability and Lipinski score. Thirteen compounds were active at 10 \u00b5M against both somules and adults (6d, 6f, 6i\u20136l, 6n\u20136p, 6s, 6r\u2019, 6t\u2019 and 6w). Against somules, the majority caused degeneracy and\/or death after 72 h; whereas against adult parasites, five compounds (6l, 6d, 6f, 6r\u2019 and 6s) elicited degeneracy, tegumental (surface) damage and\/or death. Strongest potency against both developmental stages was recorded for compounds possessing n-butyl or isobutyl as a linker, and a pentafluorophenyl group on triazole. Apart from five compounds for which anti-parasite activity tracked with toxicity to HepG2 cells, there was apparently no toxicity to HepG2 cells (EC50 values \u226550 \u00b5M). The data overall suggest that phthaloyl-triazole compounds are favorable synthons for additional studies as anti-schistosomals.<\/jats:p>","DOI":"10.3390\/ph13020025","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T11:28:31Z","timestamp":1580729311000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Synthesis and Bioactivity of Phthalimide Analogs as Potential Drugs to Treat Schistosomiasis, a Neglected Disease of Poverty"],"prefix":"10.3390","volume":"13","author":[{"given":"Snigdha","family":"Singh","sequence":"first","affiliation":[{"name":"Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College, University of Delhi, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"El-Sakkary","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle E.","family":"Skinner","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prem Prakash","family":"Sharma","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College, University of Delhi, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Ottilie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yevgeniya","family":"Antonova-Koch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashant","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Chemistry, SRM University, Delhi-NCR, Sonepat, Haryana 131029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4049-2113","authenticated-orcid":false,"given":"Elizabeth","family":"Winzeler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Poonam","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Miranda House, University of Delhi, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor R.","family":"Caffrey","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2133-8847","authenticated-orcid":false,"given":"Brijesh","family":"Rathi","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College, University of Delhi, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,3]]},"reference":[{"key":"ref_1","unstructured":"Rollinson, D., and Simpson, A.J.G. 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