dc.creatorAlberca, Lucas Nicolás
dc.creatorChuguransky, Sara Rocío
dc.creatorAlvarez, Cora Lilia
dc.creatorTalevi, Alan
dc.creatorSalas Sarduy, Emir
dc.date.accessioned2021-08-31T18:35:03Z
dc.date.accessioned2022-10-15T13:14:45Z
dc.date.available2021-08-31T18:35:03Z
dc.date.available2022-10-15T13:14:45Z
dc.date.created2021-08-31T18:35:03Z
dc.date.issued2019-08-06
dc.identifierAlberca, Lucas Nicolás; Chuguransky, Sara Rocío; Alvarez, Cora Lilia; Talevi, Alan; Salas Sarduy, Emir; In silico Guided Drug Repurposing: Discovery of New Competitive and Non-competitive Inhibitors of Falcipain-2; Frontiers Media S.A.; Frontiers in Chemistry; 7; 6-8-2019; 1-20
dc.identifier2296-2646
dc.identifierhttp://hdl.handle.net/11336/139350
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/4390233
dc.description.abstractMalaria is among the leading causes of death worldwide. The emergence of Plasmodium falciparum resistant strains with reduced sensitivity to the first line combination therapy and suboptimal responses to insecticides used for Anopheles vector management have led to renewed interest in novel therapeutic options. Here, we report the development and validation of an ensemble of ligand-based computational models capable of identifying falcipain-2 inhibitors, and their subsequent application in the virtual screening of DrugBank and Sweetlead libraries. Among four hits submitted to enzymatic assays, two (odanacatib, an abandoned investigational treatment for osteoporosis and bone metastasis, and the antibiotic methacycline) confirmed inhibitory effects on falcipain-2, with Ki of 98.2 nM and 84.4 μM. Interestingly, Methacycline proved to be a non-competitive inhibitor (α = 1.42) of falcipain-2. The effects of both hits on falcipain-2 hemoglobinase activity and on the development of P. falciparum were also studied.
dc.languageeng
dc.publisherFrontiers Media S.A.
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fchem.2019.00534/full
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fchem.2019.00534
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectDRUG REPOSITIONING
dc.subjectDRUG RESCUE
dc.subjectFALCIPAIN-2
dc.subjectMALARIA
dc.subjectMETHACYCLINE
dc.subjectODANACATIB
dc.subjectPLASMODIUM FALCIPARUM
dc.subjectVIRTUAL SCREENING
dc.titleIn silico Guided Drug Repurposing: Discovery of New Competitive and Non-competitive Inhibitors of Falcipain-2
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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