{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:59:14Z","timestamp":1772117954445,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T00:00:00Z","timestamp":1600560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["IFRR 11534"],"award-info":[{"award-number":["IFRR 11534"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["UID 98937"],"award-info":[{"award-number":["UID 98937"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Currently available drugs being used to treat leishmaniasis have several shortcomings, including high toxicity, drug administration that requires hospitalization, and the emergence of parasite resistance against clinically used drugs. As a result, there is a dire need for the development of new antileishmanial drugs that are safe, affordable, and efficient. In this study, two new series of synthesized quinazolinone derivatives were investigated as potential future antileishmanial agents, by assessing their activities against the <jats:italic>Leishmania<\/jats:italic> (<jats:italic>L<\/jats:italic>.) <jats:italic>donovani<\/jats:italic> and <jats:italic>L.\u00a0major<\/jats:italic> species. The cytotoxicity profiles of these derivatives were assessed in vitro on Vero cells. The compounds were found to be safer and without any toxic activities against mammalian cells, compared to the reference drug, halofuginone, a clinical derivative of febrifugine. However, they had demonstrated poor antileishmanial growth inhibition efficacies. The two compounds that had been found the most active were the mono quinazolinone <jats:bold>2d<\/jats:bold> and the bisquinazolinone <jats:bold>5b<\/jats:bold> with growth inhibitory efficacies of 35% and 29% for the <jats:italic>L.\u00a0major<\/jats:italic> and <jats:italic>L.\u00a0donovani<\/jats:italic> 9515 promastigotes, respectively. These outcomes had suggested structural redesign, <jats:italic>inter alia<\/jats:italic> the inclusion of polar groups on the quinazolinone ring, to potentially generate novel quinazolinone derivatives, endowed with effective antileishmanial potential.<\/jats:p>","DOI":"10.1111\/cbdd.13790","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T04:10:53Z","timestamp":1600661453000},"page":"383-398","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Synthesis and in vitro antileishmanial efficacy of novel quinazolinone derivatives"],"prefix":"10.1111","volume":"97","author":[{"given":"Izak F.","family":"Prinsloo","sequence":"first","affiliation":[{"name":"Pharmaceutical Chemistry School of Pharmacy North\u2010West University Potchefstroom South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nonkululeko H.","family":"Zuma","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences North\u2010West University Potchefstroom South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine","family":"Aucamp","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences North\u2010West University Potchefstroom South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2327-0551","authenticated-orcid":false,"given":"David D.","family":"N\u2019Da","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences North\u2010West University Potchefstroom South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,20]]},"reference":[{"issue":"9","key":"e_1_2_10_2_1","first-page":"1213","article-title":"Isolation of cycloeucalenol from Boophone disticha and evaluation of its cytotoxicity","volume":"8","author":"Adewusi E. A.","year":"2013","journal-title":"Natural Products Communications"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo01015a038"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules14083037"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.10.022"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.11.039"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.endeavour.2008.07.001"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-108-6_5"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.2445"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf501351r"},{"key":"e_1_2_10_11_1","first-page":"4054","article-title":"A parasite rescue and transformation assay for antileishmanial screening against intracellular Leishmania donovani amastigotes in THP1 human acute monocytic leukemia cell line","volume":"70","author":"Jain S. K.","year":"2012","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.3.1169-1176.2005"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.10.007"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.03.031"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules201119673"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11164-013-1131-2"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2014.02.040"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2006.07.098"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2015.1135298"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.09.028"},{"issue":"10","key":"e_1_2_10_21_1","first-page":"2405","article-title":"Synthesis of 6, 6\u2032\u2010methylenebisquinazolinones and 7, 7\u2032\u2010methylenebis\u20101, 4\u2010benzodiazepine\u20102, 5\u2010diones","volume":"34","author":"Reddy L. M.","year":"2002","journal-title":"ChemInform"},{"issue":"4","key":"e_1_2_10_22_1","first-page":"635","article-title":"Antibacterial, antifungal and antifeedant activity of quinazolinonyl\u2010\u03b2\u2010lactams\/quinazolinones and bis (quinazolinonyl\u2010\u03b2\u2010lactams)","volume":"3","author":"Reddy P.","year":"2010","journal-title":"Rasayan Journal of Chemistry"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000675"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-017-2028-5"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2013.755515"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2015.973850"},{"key":"e_1_2_10_27_1","unstructured":"World Health Organization (WHO). (2019a).Leishmaniasis: Epidemiological situation.https:\/\/www.who.int\/leishmaniasis\/burden\/en\/. [Date of accessed: 9 February 2020]."},{"key":"e_1_2_10_28_1","unstructured":"WHO. (2019b).Leishmaniasis: What is leishmaniasis?https:\/\/www.who.int\/leishmaniasis\/disease\/en\/. [Date of accessed: 9 February 2020]"},{"key":"e_1_2_10_29_1","unstructured":"World Health Organization (WHO). (2020a).Fact sheets: Detail: Leishmaniasis. Retrieved from https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/leishmaniasishttps:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/leishmaniasis. [Date accessed: 06 November 2019]"},{"key":"e_1_2_10_30_1","unstructured":"World Health Organization (WHO). (2020b).Global Health Observatory (GHO) data: Leishmaniasis.https:\/\/www.who.int\/gho\/neglected_diseases\/leishmaniasis\/en\/. [Date of accessed: 4 June 2020]"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2017.10.003"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.11.053"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2010.05.040"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.13790","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cbdd.13790","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.13790","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T17:39:34Z","timestamp":1693762774000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.13790"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,20]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1111\/cbdd.13790"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.13790","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,20]]},"assertion":[{"value":"2020-05-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}