Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-Oxide derivatives
This article belongs to the Special Issue Recent Trends on Enzymes Inhibitors and Activators in Drug Research II
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| Format: | article |
| Language: | English |
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2019
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| Online Access: | https://hdl.handle.net/20.500.12008/28671 |
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| _version_ | 1868890232134303744 |
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| author | Ferraro, Florencia |
| author2 | Merlino Mellognio, Alicia Beatriz Gil, Jorge Cerecetto, Hugo Corvo, Ileana Cabrera Cedrés, Mauricio Andrés |
| author2_role | author author author author author |
| author_browse | Cabrera Cedrés, Mauricio Andrés Cerecetto, Hugo Corvo, Ileana Ferraro, Florencia Gil, Jorge Merlino Mellognio, Alicia Beatriz |
| author_facet | Ferraro, Florencia Merlino Mellognio, Alicia Beatriz Gil, Jorge Cerecetto, Hugo Corvo, Ileana Cabrera Cedrés, Mauricio Andrés |
| author_role | author |
| collection | COLIBRI |
| dc.contributor.none.fl_str_mv | Ferraro Florencia, Universidad de la República (Uruguay). CENUR. Merlino Mellognio Alicia Beatriz, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica. Gil Jorge, Universidad de la República (Uruguay). CENUR. Cerecetto Hugo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares. Corvo Ileana, Universidad de la República (Uruguay). CENUR. Cabrera Cedrés Mauricio Andrés, Universidad de la República (Uruguay). CENUR. |
| dc.creator.none.fl_str_mv | Ferraro, Florencia Merlino Mellognio, Alicia Beatriz Gil, Jorge Cerecetto, Hugo Corvo, Ileana Cabrera Cedrés, Mauricio Andrés |
| dc.date.none.fl_str_mv | 2019 2021-07-22T13:30:26Z 2021-07-22T13:30:26Z |
| dc.format.none.fl_str_mv | 19 h. application/pdf |
| dc.identifier.none.fl_str_mv | Ferraro, F, Merlino Mellognio, A, Gil, J, y otros "Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-Oxide derivatives". Molecules. [en línea] 2019, 24(13): 2348. DOI: 10.3390/molecules24132348 1420-3049 https://hdl.handle.net/20.500.12008/28671 10.3390/molecules24132348 |
| dc.language.none.fl_str_mv | en eng |
| dc.publisher.none.fl_str_mv | MDPI |
| dc.relation.none.fl_str_mv | Molecules, 2019, 24(13): 2348 |
| dc.rights.none.fl_str_mv | info:eu-repo/semantics/openAccess Licencia Creative Commons Atribución (CC - By 4.0) |
| dc.source.none.fl_str_mv | reponame:COLIBRI instname:Universidad de la República instacron:Universidad de la República |
| dc.subject.none.fl_str_mv | Fasciola hepatica Cathepsin L Quinoxaline 1,4-di-N-oxides Small molecule inhibitors Molecular docking |
| dc.title.none.fl_str_mv | Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-Oxide derivatives |
| dc.type.none.fl_str_mv | Artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| description | This article belongs to the Special Issue Recent Trends on Enzymes Inhibitors and Activators in Drug Research II |
| eu_rights_str_mv | openAccess |
| format | article |
| id | anni_f2b256dde539f78fc8a2222f7f2eb7d4 |
| identifier_str_mv | Ferraro, F, Merlino Mellognio, A, Gil, J, y otros "Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-Oxide derivatives". Molecules. [en línea] 2019, 24(13): 2348. DOI: 10.3390/molecules24132348 1420-3049 10.3390/molecules24132348 |
| instacron_str | Universidad de la República |
| institution | Universidad de la República |
| instname_str | Universidad de la República |
| language | eng |
| language_invalid_str_mv | en |
| network_acronym_str | anni |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/28671 |
| publishDate | 2019 |
| publishDateSort | 2019 |
| publisher.none.fl_str_mv | MDPI |
| reponame_str | COLIBRI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
| spelling | Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-Oxide derivativesFerraro, FlorenciaMerlino Mellognio, Alicia BeatrizGil, JorgeCerecetto, HugoCorvo, IleanaCabrera Cedrés, Mauricio AndrésFasciola hepaticaCathepsin LQuinoxaline 1,4-di-N-oxidesSmall molecule inhibitorsMolecular dockingThis article belongs to the Special Issue Recent Trends on Enzymes Inhibitors and Activators in Drug Research IIInfections caused by Fasciola species are widely distributed in cattle and sheep causing significant economic losses, and are emerging as human zoonosis with increasing reports of human cases, especially in children in endemic areas. The current treatment is chemotherapeutic, triclabendazole being the drug of preference since it is active against all parasite stages. Due to the emergence of resistance in several countries, the discovery of new chemical entities with fasciolicidal activity is urgently needed. In our continuous search for new fasciolicide compounds, we identified and characterized six quinoxaline 1,4-di-N-oxide derivatives from our in-house library. We selected them from a screening of novel inhibitors against FhCL1 and FhCL3 proteases, two essential enzymes secreted by juvenile and adult flukes. We report compounds C7, C17, C18, C19, C23, and C24 with an IC50 of less than 10 µM in at least one cathepsin. We studied their binding kinetics in vitro and their enzyme-ligand interactions in silico by molecular docking and molecular dynamic (MD) simulations. These compounds readily kill newly excysted juveniles in vitro and have low cytotoxicity in a Hep-G2 cell line and bovine spermatozoa. Our findings are valuable for the development of new chemotherapeutic approaches against fascioliasis, and other pathologies involving cysteine proteases.MDPIFerraro Florencia, Universidad de la República (Uruguay). CENUR.Merlino Mellognio Alicia Beatriz, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica.Gil Jorge, Universidad de la República (Uruguay). CENUR.Cerecetto Hugo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.Corvo Ileana, Universidad de la República (Uruguay). CENUR.Cabrera Cedrés Mauricio Andrés, Universidad de la República (Uruguay). CENUR.2021-07-22T13:30:26Z2021-07-22T13:30:26Z2019Artículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion19 h.application/pdfFerraro, F, Merlino Mellognio, A, Gil, J, y otros "Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-Oxide derivatives". Molecules. [en línea] 2019, 24(13): 2348. DOI: 10.3390/molecules241323481420-3049https://hdl.handle.net/20.500.12008/2867110.3390/molecules24132348reponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaenengMolecules, 2019, 24(13): 2348Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)oai:colibri.udelar.edu.uy:20.500.12008/286712026-04-14T10:09:42Z |
| spellingShingle | Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-Oxide derivatives Ferraro, Florencia Fasciola hepatica Cathepsin L Quinoxaline 1,4-di-N-oxides Small molecule inhibitors Molecular docking |
| status_str | publishedVersion |
| title | Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-Oxide derivatives |
| title_full | Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-Oxide derivatives |
| title_fullStr | Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-Oxide derivatives |
| title_full_unstemmed | Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-Oxide derivatives |
| title_short | Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-Oxide derivatives |
| title_sort | Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-Oxide derivatives |
| topic | Fasciola hepatica Cathepsin L Quinoxaline 1,4-di-N-oxides Small molecule inhibitors Molecular docking |
| url | https://hdl.handle.net/20.500.12008/28671 |