{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T18:56:08Z","timestamp":1789325768855,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Leishmaniasis is a major vector\u2010borne parasitic disease that affects thousands of people in tropical and subtropical developing countries. In 2019 alone, it killed 26,000\u201365,000 individuals. Leishmaniasis is curable, yet its eradication and elimination are hampered by major hurdles, such as the availability of only a handful of clinical toxic drugs and the emergence of pathogenic resistance against them. This underscores the imperative need for new and effective antileishmanial drugs. In search for such agents, we synthesized and evaluated the in vitro antileishmanial potential of a small library of benzothiadiazine derivatives by assessing their activity against the promastigotes of three strains of <jats:italic>Leishmania<\/jats:italic> and toxicity in healthy cells. The derivatives were found to have no toxicity to the mammalian cells and were, in general, active against all parasites. The benzothiadiazine derivative <jats:bold>1e<\/jats:bold>, 3\u2010methyl\u20102\u2010[3\u2010(trifluoromethyl)benzyl]\u20102<jats:italic>H<\/jats:italic>\u2010benzo[<jats:italic>e<\/jats:italic>][1,2,4]thiadiazine 1,1\u2010dioxide, was found to be the most active (IC<jats:sub>50<\/jats:sub>, 0.2\u2009\u03bcM) against <jats:italic>Leishmania major<\/jats:italic>, responsible for the most prevalent disease form, cutaneous leishmaniasis. Conversely, benzothiadiazine <jats:bold>2c<\/jats:bold>, 2\u2010(4\u2010bromobenzyl)\u20103\u2010phenyl\u20102<jats:italic>H<\/jats:italic>\u2010benzo[<jats:italic>e<\/jats:italic>][1,2,4]thiadiazine 1,1\u2010dioxide, was the most potent (IC<jats:sub>50<\/jats:sub>, 6.5\u2009\u03bcM) against <jats:italic>Leishmania donovani<\/jats:italic>, a causative strain of the lethal visceral leishmaniasis. Both compounds stand as antipromastigote hits for further lead investigation into their potential to act as new antileishmanial agents.<\/jats:p>","DOI":"10.1002\/ardp.202000280","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T14:07:40Z","timestamp":1611583660000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Synthesis and in vitro antileishmanial efficacy of novel benzothiadiazine\u20101,1\u2010dioxide derivatives"],"prefix":"10.1002","volume":"354","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1969-8029","authenticated-orcid":false,"given":"Daisy K.","family":"Mangwegape","sequence":"first","affiliation":[{"name":"Pharmaceutical Chemistry, School of Pharmacy North\u2010West University  Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9481-1602","authenticated-orcid":false,"given":"Nonkululeko H.","family":"Zuma","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences North\u2010West University  Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-5532","authenticated-orcid":false,"given":"Janine","family":"Aucamp","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences North\u2010West University  Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2327-0551","authenticated-orcid":false,"given":"David D.","family":"N'Da","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences North\u2010West University  Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"WHO 2020"},{"key":"e_1_2_8_3_1","unstructured":"WHO 2019"},{"key":"e_1_2_8_4_1","unstructured":"WHO 2019"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.11120.1"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006052"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005641"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2009.05.010"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2017.02.063"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2014.01.072"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201900079"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/ml400447v"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4OB01849D"},{"key":"e_1_2_8_11_3","doi-asserted-by":"publisher","DOI":"10.3390\/md13095784"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/co500125n"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.11.039"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10870-009-9643-8"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(00)00129-0"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441003605098"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1032"},{"key":"e_1_2_8_18_1","first-page":"133","volume-title":"Advances in Cancer Research","author":"Goodwin R. J. A.","year":"2017"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4683"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci034243x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci200387c"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4683"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1309\/F0LPBC27FEDQA7RQ"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.7241\/ourd.20131.09"},{"key":"e_1_2_8_23_3","doi-asserted-by":"publisher","DOI":"10.1089\/vbz.2011.0844"},{"key":"e_1_2_8_23_4","doi-asserted-by":"publisher","DOI":"10.4038\/sljid.v9i1.8238"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.4.818"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00548-09"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01788"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr950066q"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.4.13"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-108-6_5"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2015.02.011"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202000280","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ardp.202000280","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202000280","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T13:19:38Z","timestamp":1693574378000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.202000280"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,25]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1002\/ardp.202000280"],"URL":"https:\/\/doi.org\/10.1002\/ardp.202000280","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,25]]},"assertion":[{"value":"2020-07-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2000280"}}