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Current treatments that are in clinical use are expensive, have toxic side effects, and are facing parasitic resistance. Therefore, new drugs are urgently required. In the quest for new, safe, and cost\u2010effective drugs, a series of novel ethylene glycol derivatives of nitrofurantoin was synthesised and the in vitro antileishmanial efficacy of the compounds tested against <jats:italic>Leishmania donovani<\/jats:italic> and <jats:italic>Leishmania major<\/jats:italic> strains. Arylated ethylene glycol derivatives were found to be the most potent, with submicromolar activity up to 294\u2010fold greater than the parent compound nitrofurantoin. Analogues <jats:bold>2j<\/jats:bold> and <jats:bold>2k<\/jats:bold> had the best antipromastigote activities with submicromolar IC<jats:sub>50<\/jats:sub> values against <jats:italic>L. major<\/jats:italic> IR\u2010173 and antimonial\u2010resistant <jats:italic>L. donovani<\/jats:italic> 9515 strains.<\/jats:p>","DOI":"10.1002\/ardp.202200529","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T05:43:37Z","timestamp":1676007817000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Exploration of ethylene glycol linked nitrofurantoin derivatives against <i>Leishmania<\/i>: Synthesis and in vitro activity"],"prefix":"10.1002","volume":"356","author":[{"given":"Keitumetsi","family":"Ndlovu","sequence":"first","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences North\u2010West University Potchefstroom South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Kannigadu","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"}]},{"given":"Helena D. 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