{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T20:18:50Z","timestamp":1782245930100,"version":"3.54.5"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T00:00:00Z","timestamp":1609113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007637","name":"Colciencias","doi-asserted-by":"crossref","award":["727-2015"],"award-info":[{"award-number":["727-2015"]}],"id":[{"id":"10.13039\/100007637","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Colciencias (MinCiencias)","award":["Project 110177758192 - Grant 777-2017"],"award-info":[{"award-number":["Project 110177758192 - Grant 777-2017"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Leishmaniasis is a neglected, parasitic tropical disease caused by an intracellular protozoan from the genus <jats:italic>Leishmania<\/jats:italic>. Quinoline alkaloids, secondary metabolites found in plants from the Rutaceae family, have antiparasitic activity against <jats:italic>Leishmania<\/jats:italic> sp. <jats:italic>N<\/jats:italic>-methyl-8-methoxyflindersin (<jats:bold>1<\/jats:bold>), isolated from the leaves of <jats:italic>Raputia heptaphylla<\/jats:italic> and also known as 7-methoxy-2,2-dimethyl-2H,5H,6H-pyran[3,2-c]quinolin-5-one, shows antiparasitic activity against <jats:italic>Leishmania<\/jats:italic> promastigotes and amastigotes. This study used <jats:italic>in silico<\/jats:italic> tools to identify synthetic quinoline alkaloids having structure similar to that of compound <jats:bold>1<\/jats:bold> and then tested these quinoline alkaloids for their <jats:italic>in vitro<\/jats:italic> antiparasitic activity against <jats:italic>Leishmania (Viannia) panamensis<\/jats:italic>, <jats:italic>in vivo<\/jats:italic> therapeutic response in hamsters suffering from experimental cutaneous leishmaniasis (CL), and <jats:italic>ex vivo<\/jats:italic> immunomodulatory potential in healthy donors\u2019 human peripheral blood (monocyte)-derived macrophages (hMDMs). Compounds <jats:bold>1<\/jats:bold> (natural), <jats:bold>2<\/jats:bold> (synthetic), and <jats:bold>8<\/jats:bold> (synthetic) were effective against intracellular promastigotes (9.9, 3.4, and 1.6 \u03bcg\/mL medial effective concentration [EC<jats:sub>50<\/jats:sub>], respectively) and amastigotes (5.07, 7.94, and 1.91 \u03bcg\/mL EC<jats:sub>50<\/jats:sub>, respectively). Compound <jats:bold>1<\/jats:bold> increased nitric oxide production in infected hMDMs and triggered necrosis-related ultrastructural alterations in intracellular amastigotes, while compound <jats:bold>2<\/jats:bold> stimulated oxidative breakdown in hMDMs and caused ultrastructural alterations in the parasite 4 h posttreatment, and compound <jats:bold>8<\/jats:bold> failed to induce macrophage modulation but selectively induced apoptosis of infected hMDMs and alterations in the intracellular parasite ultrastructure. In addition, synthetic compounds <jats:bold>2<\/jats:bold> and <jats:bold>8<\/jats:bold> improved the health of hamsters suffering from experimental CL, without evidence of treatment-associated adverse toxic effects. Therefore, synthetic compounds <jats:bold>2<\/jats:bold> and <jats:bold>8<\/jats:bold> are potential therapeutic candidates for topical treatment of CL.<\/jats:p>","DOI":"10.1371\/journal.pone.0243392","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T20:04:40Z","timestamp":1609185880000},"page":"e0243392","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Antileishmanial activity of synthetic analogs of the naturally occurring quinolone alkaloid N-methyl-8-methoxyflindersin"],"prefix":"10.1371","volume":"15","author":[{"given":"Elaine","family":"Torres Suarez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Susana","family":"Granados-Falla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Mar\u00eda","family":"Robledo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Murillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulieth","family":"Upegui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2947-7796","authenticated-orcid":true,"given":"Gabriela","family":"Delgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,28]]},"reference":[{"key":"pone.0243392.ref001","article-title":"Leishmaniasis worldwide and global estimates of its incidence.","author":"J Alvar","year":"2012","journal-title":"PLoS ONE."},{"key":"pone.0243392.ref002","article-title":"Global burden of cutaneous leishmaniasis: A cross-sectional analysis from the Global Burden of Disease Study 2013.","author":"C Karimkhani","year":"2016","journal-title":"Lancet Infect Dis."},{"key":"pone.0243392.ref003","article-title":"Leishmaniasis: a review.","author":"E Torres-Guerrero","year":"2017","journal-title":"F1000Research"},{"key":"pone.0243392.ref004","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1590\/S0074-02762003000700001","article-title":"Leishmanial Infection: Analysis of its First Steps.","author":"MC De Almeida","year":"2003","journal-title":"A Review. 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