{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T01:43:19Z","timestamp":1772674999371,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T00:00:00Z","timestamp":1522108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>There is an urgent need for the discovery of new antileishmanial drugs with a new mechanism of action. Type 2 NADH dehydrogenase from Leishmania infantum (LiNDH2) is an enzyme of the parasite\u2019s respiratory system, which catalyzes the electron transfer from NADH to ubiquinone without coupled proton pumping. In previous studies of the related NADH: ubiquinone oxidoreductase crystal structure from Saccharomyces cerevisiae, two ubiquinone-binding sites (UQI and UQII) were identified and shown to play an important role in the NDH-2-catalyzed oxidoreduction reaction. Based on the available structural data, we developed a three-dimensional structural model of LiNDH2 using homology detection methods and performed an in silico virtual screening campaign to search for potential inhibitors targeting the LiNDH2 ubiquinone-binding site 1\u2014UQI. Selected compounds displaying favorable properties in the computational screening experiments were assayed for inhibitory activity in the structurally similar recombinant NDH-2 from S. aureus and leishmanicidal activity was determined in the wild-type axenic amastigotes and promastigotes of L. infantum. The identified compound, a substituted 6-methoxy-quinalidine, showed promising nanomolar leishmanicidal activity on wild-type axenic promastigotes and amastigotes of L. infantum and the potential for further development.<\/jats:p>","DOI":"10.3390\/molecules23040772","type":"journal-article","created":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T12:17:24Z","timestamp":1522153044000},"page":"772","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["In Silico Discovery of a Substituted 6-Methoxy-quinalidine with Leishmanicidal Activity in Leishmania infantum"],"prefix":"10.3390","volume":"23","author":[{"given":"Strahinja","family":"Stevanovi\u0107","sequence":"first","affiliation":[{"name":"Center of Multidisciplinary Research, Institute of Nuclear Sciences \u201cVin\u010da\u201d, University of Belgrade, 11001 Belgrade, Serbia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6645-9231","authenticated-orcid":false,"given":"Andrej","family":"Perdih","sequence":"additional","affiliation":[{"name":"National Institute of Chemistry, Hajdrihova 19, 1001 Ljubljana, Slovenia"}]},{"given":"Milan","family":"Sen\u0107anski","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Research, Institute of Nuclear Sciences \u201cVin\u010da\u201d, University of Belgrade, 11001 Belgrade, Serbia"}]},{"given":"Sanja","family":"Gli\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Research, Institute of Nuclear Sciences \u201cVin\u010da\u201d, University of Belgrade, 11001 Belgrade, Serbia"}]},{"given":"Margarida","family":"Duarte","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto and IBMC-Institute for Molecular and Cell Biology, 4099-002 Porto, Portugal"}]},{"given":"Ana","family":"Tom\u00e1s","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto and IBMC-Institute for Molecular and Cell Biology, 4099-002 Porto, Portugal"},{"name":"ICBAS, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4099-002 Porto, Portugal"}]},{"given":"Filipa","family":"Sena","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, 1099-085 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3761-743X","authenticated-orcid":false,"given":"Filipe","family":"Sousa","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, 1099-085 Oeiras, Portugal"}]},{"given":"Manuela","family":"Pereira","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, 1099-085 Oeiras, Portugal"},{"name":"University of Lisbon, Faculty of Sciences, BioISI-Biosystems & Integrative Sciences Institute, Campo Grande, C8, 1749-016 Lisboa, Portugal"}]},{"given":"Tom","family":"Solmajer","sequence":"additional","affiliation":[{"name":"National Institute of Chemistry, Hajdrihova 19, 1001 Ljubljana, Slovenia"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,27]]},"reference":[{"key":"ref_1","unstructured":"WHO (2018, February 05). 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