| Título: | Multidrug Resistance Reversal Effects of Aminated Thioxanthones and Interaction with Cytochrome P450 3A4 |
| Autores: |
Palmeira, Andreia; Departamento de Química, Laboratório de Química Orgânica e Farmacêutica, Faculdade de Farmácia, Universidade do Porto, Rua Anibal Cunha 164, 4050-047, Porto, Portugal Sousa, Maria Emília; Departamento de Química, Laboratório de Química Orgânica e Farmacêutica, Faculdade de Farmácia, Universidade do Porto, Rua Anibal Cunha 164, 4050-047, Porto, Portugal Fernandes, Miguel X; Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9000-390, Funchal, Portugal Pinto, Madalena M.; Departamento de Química, Laboratório de Química Orgânica e Farmacêutica, Faculdade de Farmácia, Universidade do Porto, Rua Anibal Cunha 164, 4050-047, Porto, Portugal Vasconcelos, M. Helena; Cancer Drug Resistance Group, IPATIMUP – Institute of Molecular Pathology and Immunology of the University of Porto, Portugal, Rua Dr Roberto Frias s/n, 4200-465 Porto, Portugal |
| Fecha: | 2011-12-05 |
| Publicador: | Journal of Pharmacy and Pharmaceutical Sciences |
| Fuente: |
 |
| Tipo: |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| Tema: | No aplica |
| Descripción: | Purpose. Aminated thioxanthones have recently been described as dual-acting agents: growth inhibitors of leukemia cell lines and P-glycoprotein (P-gp) inhibitors. To evaluate the selectivity profile of thioxanthones as inhibitors of multidrug resistance (MDR), their interaction with other ABC transporters, which were found to have a strong correlation with multidrug resistance, such as multidrug resistant proteins 1 (MRP1), 2 (MRP2) and 3 (MRP3) and breast cancer resistance protein (BCRP) was also evaluated. The interaction of thioxanthones with cytochrome P450 3A4 (CYP3A4) together with the prediction of their binding conformations and metabolism sites was also investigated. Methods. The UIC2 monoclonal antibody-labelling assay was performed using P-gp overexpressing leukemia cells, K562Dox, incubated with eight thioxanthonic derivatives, in order to confirm their P-gp inhibitory activity. A colorimetric-based ATPase assay using membrane vesicles from mammalian cells overexpressing a selected human ABC transporter protein (P-gp, MRP1, MRP2, MRP3, or BCRP) was performed. To verify if some of the thioxanthonic derivatives were substrates or inhibitors of CYP3A4, a luciferin-based luminescence assay was performed. Finally, the in silico prediction of the most probable metabolism sites and docking studies of thioxanthones on CYP3A4 binding site were investigated. Results. Thioxanthones interacted not only with P-gp but also with MRP and BCRP transporters. These compounds also interfere with CYP3A4 activity in vitro, in accordance with the in silico prediction. Conclusion. Thioxanthonic derivatives are multi-target compounds. A better characterization of the interactions of these compounds with classical resistance mechanisms may possibly identify improved treatment applications. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page. |
| Idioma: | Inglés |
1 The Impact of Electronic Prescribing on the Professionalization of Community Pharmacists: A Qualitative Study of Pharmacists’ Perception por Motulsky, Aude; Université de Montréal,Winslade, Nancy; McGill University,Tamblyn, Robyn; McGill University,Sicotte, Claude; Université de Montréal | 6 Effect of Inflammation on Molecular Targets and Drug Transporters por Hanafy, Sherif; Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada,El-Kadi, Ayman O.S.,Jamali, Fakhreddin; Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada |
2 Statins Against Drug-Induced Nephrotoxicity por Dashti-Khavidaki, Simin; Tehran University of Medical Sciences,Moghaddas, Azadeh; Tehran University of Medical Sciences,,Heydari, Behrooz; Tehran University of Medical Sciences,,Khalili, Hossein; Tehran University of Medical Sciences,lessan-Pezeshki, Mahboob; Tehran University of Medical Sciences,,Lessan-Pezeshki, Mahbooh; Tehran University of Medical Sciences | 7 |
3 Hepatotoxic Botanicals - An Evidence-based Systematic Review por Abdualmjid, Reem J; University of Alberta,Sergi, Consolato; University of Alberta | 8 |
4 The Decrease in Farnesoid X Receptor, Pregnane X Receptor and Constitutive Androstane Receptor in the Liver after Intestinal Ischemia-Reperfusion por Ogura, Jiro,Terada, Yusuke,Tsujimoto, Takashi,Koizumi, Takahiro,Kuwayama, Kaori,Maruyama, Hajime,Fujikawa, Asuka,Takaya, Atsushi,Kobayashi, Masaki,Itagaki, Shirou,Takahashi, Natsuko,Hirano, Takeshi,Yamaguchi, Hiroaki,Iseki, Ken | 9 Functional Food and Nutraceutical Registration Processes in Japan and China: A Diffusion of Innovation Perspective por Patel, Darshika; University of Auckland,Dufour, Yvon; University of Auckland,Domigan, Neil; Auctus Limited |
5 HPLC Analysis of Mesembrine-Type Alkaloids in Sceletium Plant Material Used as An African Traditional Medicine por Patnala, Srinivas; Rhodes University,Kanfer, Isadore; Faculty of Pharmacy, Rhodes University | 10 Inhibition of Human Cytochrome P450 Metabolism by Blended Herbal Products and Vitamins por Tam, Teresa W; Centre for Research in Biopharmaceuticals and Biotechnology, University of Ottawa, Ottawa, ON,Akhtar, Humayoun; Guelph Food Research Centre, Agriculture and Agri-Food Canada, Guelph, ON,Arnason, John Thor; Centre for Research in Biopharmaceuticals and Biotechnology, University of Ottawa, Ottawa, ON,Cvijovic, Kosta; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON,Boon, Heather; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON,Cameron, D William; Faculty of Medicine, Univeristy of Ottawa, Ottawa, ON,Drouin, Cathy E; Centre for Research in Biopharmaceuticals and Biotechnology, University of Ottawa, Ottawa, ON,Jaeger, Walter; Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna,Tsuyuki, Ross T; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB,Vohra, Sunita; CARE Program, Faculty of Medicine and School of Public Health, University of Alberta, Edmonton, AB,Foster, Brian C; Office of Science, Therapeutic Products Directorate, Health Canada, Ottawa, ON |