Characterization of potent ABCG2 inhibitor derived from chromone: from the mechanism of inhibition to human extracellular vesicles for drug delivery

dc.creatorValdameri, Glaucio
dc.creatorKita, Diogo Henrique
dc.creatorDutra, Julia de Paula
dc.creatorGomes, Diego Lima
dc.creatorTonduru, Arun Kumar
dc.creatorKronenberger, Thales
dc.creatorGavinho, Bruno
dc.creatorRossi, Izadora Volpato
dc.creatorCarvalho, Mariana Mazetto de
dc.creatorPérès, Basile
dc.creatorZattoni, Ingrid Fatima
dc.creatorRego, Fabiane Gomes de Moraes
dc.creatorPicheth, Geraldo
dc.creatorFreitas, Rilton Alves de
dc.creatorPoso, Antti
dc.creatorAmbudkar, Suresh V.
dc.creatorRamírez, Marcel Ivan
dc.creatorBoumendjel, Ahcène
dc.creatorMoure, Vivian Rotuno
dc.date2023-05-22T15:13:32Z
dc.date2023-05-22T15:13:32Z
dc.date2023
dc.date.accessioned2023-09-26T23:09:41Z
dc.date.available2023-09-26T23:09:41Z
dc.identifierVALDAMERI, Glaucio et al. Characterization of potent ABCG2 inhibitor derived from chromone: from the mechanism of inhibition to human extracellular vesicles for drug delivery. Pharmaceutics, v. 15, n. 1259, p. 1-17, 2023.
dc.identifier1999-4923
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/58551
dc.identifierhttps://doi.org/10.3390/ pharmaceutics15041259
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8887526
dc.descriptionInhibition of ABC transporters is a promising approach to overcome multidrug resistance in cancer. Herein, we report the characterization of a potent ABCG2 inhibitor, namely, chromone 4a (C4a). Molecular docking and in vitro assays using ABCG2 and P-glycoprotein (P-gp) expressing membrane vesicles of insect cells revealed that C4a interacts with both transporters, while showing selectivity toward ABCG2 using cell-based transport assays. C4a inhibited the ABCG2-mediated efflux of different substrates and molecular dynamic simulations demonstrated that C4a binds in the Ko143-binding pocket. Liposomes and extracellular vesicles (EVs) of Giardia intestinalis and human blood were used to successfully bypass the poor water solubility and delivery of C4a as assessed by inhibition of the ABCG2 function. Human blood EVs also promoted delivery of the well-known P-gp inhibitor, elacridar. Here, for the first time, we demonstrated the potential use of plasma circulating EVs for drug delivery of hydrophobic drugs targeting membrane proteins.
dc.formatapplication/pdf
dc.languagepor
dc.publisherMDPI
dc.rightsopen access
dc.subjectMembro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP
dc.subjectInibição
dc.subjectATP Binding Cassette Transporter, Subfamily G, Member 2
dc.subjectChromones
dc.subjectInhibition
dc.subjectExtracellular Vesicles
dc.subjectDrug Delivery
dc.subjectTransportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2
dc.subjectCromonas
dc.subjectInhibición
dc.subjectVesículas Extracelulares
dc.subjectLiberación de Medicamentos
dc.subjectMembre-2 de la sous-famille G des transporteurs à cassette liant l'ATP
dc.subject4H-1-Benzopyran-4-ones
dc.subjectInhibition
dc.subjectVésicules extracellulaires
dc.subjectDélivrance de médicaments
dc.subjectProteína ABCG2
dc.subjectCromonas
dc.subjectVesículas Extracelulares
dc.subjectLiberação de Medicamentos
dc.titleCharacterization of potent ABCG2 inhibitor derived from chromone: from the mechanism of inhibition to human extracellular vesicles for drug delivery
dc.typeArticle


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