{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:23:59Z","timestamp":1768562639390,"version":"3.49.0"},"reference-count":43,"publisher":"Cambridge University Press (CUP)","issue":"1","license":[{"start":{"date-parts":[[2015,11,4]],"date-time":"2015-11-04T00:00:00Z","timestamp":1446595200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["journals.cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>A selection of 1,2-disubstituted 5-nitroindazolin-3-ones (<jats:italic>1\u201319<\/jats:italic>) and 3-alkoxy-5-nitroindazoles substituted at positions 1 (<jats:italic>20\u201324<\/jats:italic>) or 2 (<jats:italic>25\u201339<\/jats:italic>) from our in-house compound library were screened <jats:italic>in vitro<\/jats:italic> against the most common curable sexually transmitted pathogen, <jats:italic>Trichomonas vaginalis<\/jats:italic>. A total of 41% of the studied molecules (16\/39) achieved a significant activity of more than 85% growth inhibition at the highest concentration assayed (100 <jats:italic>\u00b5<\/jats:italic>g mL<jats:sup>\u22121<\/jats:sup>). Among these compounds, 3-alkoxy-5-nitroindazole derivatives <jats:italic>23, 24, 25<\/jats:italic> and <jats:italic>27<\/jats:italic> inhibited parasite growth by more than 50% at 10 <jats:italic>\u00b5<\/jats:italic>g mL<jats:sup>\u22121<\/jats:sup>. In addition, the first two compounds (<jats:italic>23, 24<\/jats:italic>) still showed remarkable activity at the lowest dose tested (1 <jats:italic>\u00b5<\/jats:italic>g mL<jats:sup>\u22121<\/jats:sup>), inhibiting parasite growth by nearly 40%. Their specific activity towards the parasite was corroborated by the determination of their non-specific cytotoxicity against mammalian cells. The four mentioned compounds exhibited non-cytotoxic profiles at all of the concentrations assayed, showing a fair antiparasitic selectivity index (SI &gt; 7\u00b75). <jats:italic>In silico<\/jats:italic> studies were performed to predict pharmacokinetic properties, toxicity and drug-score using Molinspiration and OSIRIS computational tools. The current <jats:italic>in vitro<\/jats:italic> results supported by the virtual screening suggest 2-substituted and, especially, 1-substituted 3-alkoxy-5-nitroindazoles as promising starting scaffolds for further development of novel chemical compounds with the main aim of promoting highly selective trichomonacidal lead-like drugs with adequate pharmacokinetic and toxicological profiles.<\/jats:p>","DOI":"10.1017\/s0031182015001419","type":"journal-article","created":{"date-parts":[[2015,11,3]],"date-time":"2015-11-03T04:36:58Z","timestamp":1446525418000},"page":"34-40","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":9,"title":["<i>In vitro<\/i> trichomonacidal activity and preliminary <i>in silico<\/i> chemometric studies of 5-nitroindazolin-3-one and 3-alkoxy-5-nitroindazole derivatives"],"prefix":"10.1017","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8687-1100","authenticated-orcid":false,"given":"ALEXANDRA","family":"IB\u00c1\u00d1EZ-ESCRIBANO","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JUAN JOS\u00c9","family":"NOGAL-RUIZ","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ALICIA","family":"G\u00d3MEZ-BARRIO","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"VICENTE J.","family":"AR\u00c1N","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JOS\u00c9 ANTONIO","family":"ESCARIO","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2015,11,4]]},"reference":[{"key":"S0031182015001419_ref30","doi-asserted-by":"publisher","DOI":"10.1086\/338399"},{"key":"S0031182015001419_ref24","doi-asserted-by":"publisher","DOI":"10.1016\/j.mpmed.2014.04.004"},{"key":"S0031182015001419_ref36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002844"},{"key":"S0031182015001419_ref38","doi-asserted-by":"publisher","DOI":"10.1021\/jm020017n"},{"key":"S0031182015001419_ref33","unstructured":"Organic Chemistry Portal (2014). 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