| Author | Valdameri, Glaucio | |
| Author | Kita, Diogo Henrique | |
| Author | Dutra, Julia de Paula | |
| Author | Gomes, Diego Lima | |
| Author | Tonduru, Arun Kumar | |
| Author | Kronenberger, Thales | |
| Author | Gavinho, Bruno | |
| Author | Rossi, Izadora Volpato | |
| Author | Carvalho, Mariana Mazetto de | |
| Author | Pérès, Basile | |
| Author | Zattoni, Ingrid Fatima | |
| Author | Rego, Fabiane Gomes de Moraes | |
| Author | Picheth, Geraldo | |
| Author | Freitas, Rilton Alves de | |
| Author | Poso, Antti | |
| Author | Ambudkar, Suresh V. | |
| Author | Ramirez, Marcel Ivan | |
| Author | Boumendjel, Ahcène | |
| Author | Moure, Vivian Rotuno | |
| Access date | 2023-05-22T15:13:32Z | |
| Available date | 2023-05-22T15:13:32Z | |
| Document date | 2023 | |
| Citation | VALDAMERI, 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. | en_US |
| ISSN | 1999-4923 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/58551 | |
| Language | por | en_US |
| Publisher | MDPI | en_US |
| Rights | open access | en_US |
| Subject in Portuguese | Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP | en_US |
| Subject in Portuguese | Inibição | en_US |
| Title | Characterization of potent ABCG2 inhibitor derived from chromone: from the mechanism of inhibition to human extracellular vesicles for drug delivery | en_US |
| Type | Article | en_US |
| DOI | https://doi.org/10.3390/ pharmaceutics15041259 | |
| Abstract | Inhibition 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. | en_US |
| Affilliation | Universidade Federal do Paraná. Programa de Pós-Graduação em Ciências Farmacêuticas. Curitiba, PR, Brasil. / Universidade Federal do Paraná. Laboratório de Neoplasias Resistentes a Drogas. Curitiba, PR, Brasil. | en_US |
| Affilliation | Universidade Federal do Paraná. Programa de Pós-Graduação em Ciências Farmacêuticas. Curitiba, PR, Brasil. / Universidade Federal do Paraná. Laboratório de Neoplasias Resistentes a Drogas. Curitiba, PR, Brasil. / Laboratory of Cell Biology. Center for Cancer Research. National Cancer Institute. National Institutes of Health. Bethesda, Maryland, USA. | en_US |
| Affilliation | Universidade Federal do Paraná. Programa de Pós-Graduação em Ciências Farmacêuticas. Curitiba, PR, Brasil. / Universidade Federal do Paraná. Laboratório de Neoplasias Resistentes a Drogas. Curitiba, PR, Brasil. | en_US |
| Affilliation | Universidade Federal do Paraná. Programa de Pós-Graduação em Ciências Farmacêuticas. Curitiba, PR, Brasil. / Universidade Federal do Paraná. Laboratório de Neoplasias Resistentes a Drogas. Curitiba, PR, Brasil. | en_US |
| Affilliation | School of Pharmacy. Faculty of Health Sciences. University of Eastern Finland. Kuopio, Finland. | en_US |
| Affilliation | School of Pharmacy. Faculty of Health Sciences. University of Eastern Finland. Kuopio, Finland. / Institute of Pharmacy. Pharmaceutical/Medicinal Chemistry and Tübingen Center for Academic Drug Discovery & Development. Eberhard Karls University Tübingen. Tübingen, Germany. | en_US |
| Affilliation | Universidade Federal do Paraná. Programa de Pós-Graduação em Microbiologia, Parasitologia e Patologia. Curitiba, PR, Brasil. | en_US |
| Affilliation | Universidade Federal do Paraná. Programa de Pós-Graduação em Biologia Celular e Molecular. Curitiba, PR, Brasil. | en_US |
| Affilliation | Universidade Federal do Paraná. Programa de Pós-Graduação em Ciências Farmacêuticas. Laboratório de Biopolímeros. Curitiba, PR, Brasil. | en_US |
| Affilliation | Département de Pharmacochimie Moléculaire. Université Grenoble Alpes. Grenoble, France. | en_US |
| Affilliation | Universidade Federal do Paraná. Programa de Pós-Graduação em Ciências Farmacêuticas. Curitiba, PR, Brasil. / Universidade Federal do Paraná. Laboratório de Neoplasias Resistentes a Drogas. Curitiba, PR, Brasil. | en_US |
| Affilliation | Universidade Federal do Paraná. Programa de Pós-Graduação em Ciências Farmacêuticas. Curitiba, PR, Brasil. | en_US |
| Affilliation | Universidade Federal do Paraná. Programa de Pós-Graduação em Ciências Farmacêuticas. Curitiba, PR, Brasil. | en_US |
| Affilliation | Universidade Federal do Paraná. Programa de Pós-Graduação em Ciências Farmacêuticas. Laboratório de Biopolímeros. Curitiba, PR, Brasil. | en_US |
| Affilliation | School of Pharmacy. Faculty of Health Sciences. University of Eastern Finland. Kuopio, Finland. / Institute of Pharmacy. Pharmaceutical/Medicinal Chemistry and Tübingen Center for Academic Drug Discovery & Development. Eberhard Karls University Tübingen. Tübingen, Germany. | en_US |
| Affilliation | Laboratory of Cell Biology. Center for Cancer Research. National Cancer Institute. National Institutes of Health. Bethesda, Maryland, USA | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Celular. Curitiba, PR, Brasil. | en_US |
| Affilliation | Université Grenoble Alpes. INSERM. Grenoble, France. | en_US |
| Affilliation | Universidade Federal do Paraná. Programa de Pós-Graduação em Ciências Farmacêuticas. Curitiba, PR, Brasil. / Universidade Federal do Paraná. Laboratório de Neoplasias Resistentes a Drogas. Curitiba, PR, Brasil. | en_US |
| Subject | ATP Binding Cassette Transporter, Subfamily G, Member 2 | en_US |
| Subject | Chromones | en_US |
| Subject | Inhibition | en_US |
| Subject | Extracellular Vesicles | en_US |
| Subject | Drug Delivery | en_US |
| Subject in Spanish | Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 | en_US |
| Subject in Spanish | Cromonas | en_US |
| Subject in Spanish | Inhibición | en_US |
| Subject in Spanish | Vesículas Extracelulares | en_US |
| Subject in Spanish | Liberación de Medicamentos | en_US |
| Subject in French | Membre-2 de la sous-famille G des transporteurs à cassette liant l'ATP | en_US |
| Subject in French | 4H-1-Benzopyran-4-ones | en_US |
| Subject in French | Inhibition | en_US |
| Subject in French | Vésicules extracellulaires | en_US |
| Subject in French | Délivrance de médicaments | en_US |
| DeCS | Proteína ABCG2 | en_US |
| DeCS | Cromonas | en_US |
| DeCS | Vesículas Extracelulares | en_US |
| DeCS | Liberação de Medicamentos | en_US |
