{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:03:46Z","timestamp":1789787026131,"version":"4.0.1"},"reference-count":102,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,2]],"date-time":"2022-04-02T00:00:00Z","timestamp":1648857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014054","name":"Drugs for Neglected Diseases Initiative","doi-asserted-by":"publisher","award":["Resist"],"award-info":[{"award-number":["Resist"]}],"id":[{"id":"10.13039\/501100014054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>There is a need for new, cost-effective drugs to treat leishmaniasis. A strategy based on traditional medicine practiced in Bolivia led to the discovery of the 2-substituted quinoline series as a source of molecules with antileishmanial activity and low toxicity. This review documents the development of the series from the first isolated natural compounds through several hundred synthetized molecules to an optimized compound exhibiting an in vitro IC50 value of 0.2 \u00b5M against Leishmania donovani, and a selectivity index value of 187, together with in vivo activity on the L. donovani\/hamster model. Attempts to establish structure\u2013activity relationships are described, as well as studies that have attempted to determine the mechanism of action. For the latter, it appears that molecules of this series act on multiple targets, possibly including the immune system, which could explain the observed lack of drug resistance after in vitro drug pressure. We also show how nanotechnology strategies could valorize these drugs through adapted formulations and how a mechanistic targeting approach could generate new compounds with increased activity.<\/jats:p>","DOI":"10.3390\/molecules27072313","type":"journal-article","created":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T02:59:52Z","timestamp":1648954792000},"page":"2313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The Potential of 2-Substituted Quinolines as Antileishmanial Drug Candidates"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8542-6793","authenticated-orcid":false,"given":"Philippe M.","family":"Loiseau","sequence":"first","affiliation":[{"name":"Antiparasite Chemotherapy, CNRS, BioCIS, Universit\u00e9 Paris-Saclay, 92290 Chatenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2020-269X","authenticated-orcid":false,"given":"Kaluvu","family":"Balaraman","sequence":"additional","affiliation":[{"name":"Chemistry Department, Georgetown University, 37th and O Streets, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0153-910X","authenticated-orcid":false,"given":"Gillian","family":"Barratt","sequence":"additional","affiliation":[{"name":"Institute Galien Paris-Saclay, CNRS, Universit\u00e9 Paris-Saclay, 92290 Chatenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Pomel","sequence":"additional","affiliation":[{"name":"Antiparasite Chemotherapy, CNRS, BioCIS, Universit\u00e9 Paris-Saclay, 92290 Chatenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9my","family":"Durand","sequence":"additional","affiliation":[{"name":"Antiparasite Chemotherapy, CNRS, BioCIS, Universit\u00e9 Paris-Saclay, 92290 Chatenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Fr\u00e9zard","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics-ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Figad\u00e8re","sequence":"additional","affiliation":[{"name":"Chimie des Substances Naturelles, CNRS, BioCIS, Universit\u00e9 Paris-Saclay, 92290 Chatenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,2]]},"reference":[{"key":"ref_1","unstructured":"(2022, March 28). 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