{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:55:10Z","timestamp":1784116510671,"version":"3.55.0"},"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016270","name":"Global Challenges Research Fund","doi-asserted-by":"publisher","award":["MR\/P027989\/1"],"award-info":[{"award-number":["MR\/P027989\/1"]}],"id":[{"id":"10.13039\/100016270","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Cutaneous leishmaniasis (CL) is a major health problem in over 98 countries of the world, including Pakistan. The current treatments are associated with a number of adverse effects and availability problem of drugs. Therefore, there is an urgent need of easily available and cost effective treatments of CL- in Pakistan. The bioassay-guided fractionation and purification of crude extract of <jats:italic>Physalis minima<\/jats:italic> has led to the isolation of a new aminophysalin B (<jats:bold>1<\/jats:bold>), and eight known physalins, physalin B (<jats:bold>2<\/jats:bold>), 5\u00df,6\u00df-epoxyphysalin B (<jats:bold>3<\/jats:bold>), 5\u03b1-ethoxy-6\u00df-hydroxy-5,6-dihydrophysalin B (<jats:bold>4<\/jats:bold>), physalin H (<jats:bold>5<\/jats:bold>), 5\u00df,6\u00df-epoxyphysalin C (<jats:bold>6<\/jats:bold>), and physalin G (<jats:bold>7<\/jats:bold>), K (<jats:bold>8<\/jats:bold>), and D (<jats:bold>9<\/jats:bold>). It is worth noting that compound <jats:bold>1<\/jats:bold> is the second member of aminophysalin series, whereas compound <jats:bold>6<\/jats:bold> was fully characterized for the first time. The structures of compounds <jats:bold>1<\/jats:bold>\u2013<jats:bold>9<\/jats:bold> were elucidated by spectroscopic techniques Whereas, the structural assignments of compounds <jats:bold>1<\/jats:bold> and <jats:bold>8<\/jats:bold> were also supported by single-crystal X-ray diffraction studies. The anti-leishmanial activity of isolated physlains <jats:bold>1\u20139<\/jats:bold> was evaluated against <jats:italic>Leishmania major<\/jats:italic> and <jats:italic>Leishmania tropica<\/jats:italic> promastigotes. Compounds <jats:bold>2<\/jats:bold>, <jats:bold>3<\/jats:bold>, and <jats:bold>5<\/jats:bold>\u2013<jats:bold>7<\/jats:bold> (IC<jats:sub><jats:bold>50<\/jats:bold><\/jats:sub> <jats:bold>=<\/jats:bold> 9.59 \u00b1 0.27\u201323.76 \u00b1 1.10 \u03bcM) showed several-fold more potent activity against <jats:italic>L<\/jats:italic>. <jats:italic>tropca<\/jats:italic> than tested drug miltefosine (IC<jats:sub><jats:bold>50<\/jats:bold><\/jats:sub> <jats:bold>=<\/jats:bold> 42.75 \u00b1 1.03 \u03bcm) and pentamidine (IC<jats:sub>50<\/jats:sub> = 27.20 \u00b1 0.01 \u03bcM). Whereas compounds <jats:bold>2<\/jats:bold>, <jats:bold>3<\/jats:bold> and <jats:bold>5<\/jats:bold> (IC<jats:sub><jats:bold>50<\/jats:bold><\/jats:sub> <jats:bold>=<\/jats:bold> 3.04 \u00b1 1.12\u20133.76 \u00b1 0.85 \u03bcM) were found to be potent anti-leishmanial agents against <jats:italic>L<\/jats:italic>. <jats:italic>major<\/jats:italic>, several fold more active than tested standard miltefosine (IC<jats:sub><jats:bold>50<\/jats:bold><\/jats:sub> <jats:bold>=<\/jats:bold> 25.55 \u00b1 1.03 \u03bcM) and pentamidine (IC<jats:sub><jats:bold>50<\/jats:bold><\/jats:sub> <jats:bold>=<\/jats:bold> 27.20 \u00b1 0.015 \u03bcM<jats:bold>)<\/jats:bold>. Compounds <jats:bold>4<\/jats:bold> (IC<jats:sub>50<\/jats:sub> = 74.65 \u00b1 0.81 \u03bcM) and <jats:bold>7<\/jats:bold> (IC<jats:sub>50<\/jats:sub> = 39.44 \u00b1 0.65 \u03bcM) also showed potent anti-leishmanial ativity against the miltefosine-unresponsive <jats:italic>L<\/jats:italic>. <jats:italic>tropica<\/jats:italic> strain (MIL resistant) (miltefosine IC<jats:sub>50<\/jats:sub> = 169.55 \u00b1 0.78 \u03bcM). Molecular docking and predictive binding studies indicated that these inhibitors may act <jats:italic>via<\/jats:italic> targeting important enzymes of various metabolic pathways of the parasites.<\/jats:p>","DOI":"10.1371\/journal.pone.0274543","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T18:51:00Z","timestamp":1669661460000},"page":"e0274543","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Anti-leishmanial physalins\u2014Phytochemical investigation, in vitro evaluation against clinical and MIL-resistant L. tropica strains and in silico studies"],"prefix":"10.1371","volume":"17","author":[{"given":"Saira","family":"Bano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Memoona","family":"Bibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba","family":"Farooq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humaira","family":"Zafar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muniza","family":"Shaikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behram Khan","family":"Khoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8870-3581","authenticated-orcid":true,"given":"Sammer","family":"Yousuf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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