TY - JOUR AU - Schelz, Zsuzsanna AU - Abdallah, Hiba Faroug Muddather AU - Zupkó, István TI - Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance JF - ANTIBIOTICS J2 - ANTIBIOTICS-BASEL VL - 12 PY - 2023 IS - 9 PG - 30 SN - 2079-6382 DO - 10.3390/antibiotics12091468 UR - https://m2.mtmt.hu/api/publication/34165889 ID - 34165889 N1 - ISSN:2079-6382 AB - Efflux pump (EP)-mediated multidrug resistance (MDR) seems ubiquitous in bacterial infections and neoplastic diseases. The diversity and lack of specificity of these efflux mechanisms raise a great obstacle in developing drugs that modulate efflux pumps. Since developing novel chemotherapeutic drugs requires large investments, drug repurposing offers a new approach that can provide alternatives as adjuvants in treating resistant microbial infections and progressive cancerous diseases. Hydroxy-methyl-glutaryl coenzyme-A (HMG-CoA) reductase inhibitors, also known as statins, are promising agents in this respect. Originally, statins were used in the therapy of dyslipidemia and for the prevention of cardiovascular diseases; however, extensive research has recently been performed to elucidate the functions of statins in bacterial infections and cancers. The mevalonate pathway is essential in the posttranslational modification of proteins related to vital eukaryotic cell functions. In this article, a comparative review is given about the possible role of HMG-CoA reductase inhibitors in managing diseases of bacterial and neoplastic origin. Molecular research and clinical studies have proven the justification of statins in this field. Further well-designed clinical trials are urged to clarify the significance of the contribution of statins to the lower risk of disease progression in bacterial infections and cancerous diseases. LA - English DB - MTMT ER - TY - JOUR AU - Cardoso, David AU - Szemerédi, Nikoletta AU - Spengler, Gabriella AU - Mulhovo, Silva AU - dos Santos, Daniel AU - Ferreira, Maria-José TI - Exploring the Monoterpene Indole Alkaloid Scaffold for Reversing P-Glycoprotein-Mediated Multidrug Resistance in Cancer JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 14 PY - 2021 IS - 9 PG - 31 SN - 1424-8247 DO - 10.3390/ph14090862 UR - https://m2.mtmt.hu/api/publication/32287706 ID - 32287706 N1 - Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, Lisbon, 1649-003, Portugal Department of Medical Microbiology, Albert Szent-Györgyi Health Center, Faculty of Medicine, University of Szeged, Semmelweis utca 6, Szeged, 6725, Hungary Centro de Estudos Moçambicanos e de Etnociências (CEMEC), Faculdade de Ciências Naturais e Matemática, Universidade Pedagógica Campus de Lhanguene, Av. De Moçambique, Maputo, 21402161, Mozambique LAQV@REQUIMTE/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre, Porto, 4169-007, Portugal Cited By :7 Export Date: 9 June 2023 Correspondence Address: Ferreira, M.-J.U.; Research Institute for Medicines (iMed.ULisboa), Av. Prof. Gama Pinto, Portugal; email: mjuferreira@ff.ulisboa.pt Chemicals/CAS: cisplatin, 15663-27-1, 26035-31-4, 96081-74-2; doxorubicin, 23214-92-8, 25316-40-9; verapamil, 152-11-4, 52-53-9 Funding details: Fundação para a Ciência e a Tecnologia, FCT, GINOP-2.3.2-15-2016-00012, PD/BD/135291/2017, PTDC/MED-QUI/30591/2017 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, 2019/2020 Funding text 1: Funding: This study was supported by Fundação para a Ciência e a Tecnologia (FCT), Portugal (projects: PTDC/MED-QUI/30591/2017, and SAICT-PAC/0019/2015;PhD grant PD/BD/135291/2017). The study was also supported by the GINOP-2.3.2-15-2016-00012 project (University of Szeged, Hungary) and the Bilateral Portuguese–Hungarian Science & Technology Cooperation (FCT/NKFIH, 2019/2020). Funding text 2: This study was supported by Funda??o para a Ci?ncia e a Tecnologia (FCT), Portugal (projects: PTDC/MED-QUI/30591/2017, and SAICT-PAC/0019/2015; PhD grant PD/BD/135291/2017). The study was also supported by the GINOP-2.3.2-15-2016-00012 project (University of Szeged, Hungary) and the Bilateral Portuguese?Hungarian Science & Technology Cooperation (FCT/NKFIH, 2019/2020). AB - Dregamine (1), a major monoterpene indole alkaloid isolated from Tabernaemontana elegans, was submitted to chemical transformation of the ketone function, yielding 19 azines (3-21) and 11 semicarbazones (22-32) bearing aliphatic or aromatic substituents. Their structures were assigned mainly by 1D and 2D NMR (COSY, HMQC, and HMBC) experiments. Compounds 3-32 were evaluated as multidrug resistance (MDR) reversers through functional and chemosensitivity assays in a human ABCB1-transfected mouse T-lymphoma cell model, overexpressing P-glycoprotein. A significant increase of P-gp inhibitory activity was observed for most derivatives, mainly those containing azine moieties with aromatic substituents. Compounds with trimethoxyphenyl (17) or naphthyl motifs (18, 19) were among the most active, exhibiting strong inhibition at 0.2 mu M. Moreover, most of the derivatives showed selective antiproliferative effects toward resistant cells, having a collateral sensitivity effect. In drug combination assays, all compounds showed to interact synergistically with doxorubicin. Selected compounds (12, 17, 18, 20, and 29) were evaluated in the ATPase activity assay, in which all compounds but 12 behaved as inhibitors. To gather further insights on drug-receptor interactions, in silico studies were also addressed. A QSAR model allowed us to deduce that compounds bearing bulky and lipophilic substituents were stronger P-gp inhibitors. LA - English DB - MTMT ER - TY - JOUR AU - Szemerédi, Nikoletta AU - Dobiasová, Simona AU - Salardón-Jiménez, Noemi AU - Kincses, Annamária AU - Nové, Márta AU - Habibullah, Giyaullah AU - Sevilla-Hernández, Clotilde AU - Benito-Lama, Miguel AU - Alonso-Martínez, Francisco-Javier AU - Viktorová, Jitka AU - Spengler, Gabriella AU - Domínguez-Álvarez, Enrique TI - Cyano- and Ketone-Containing Selenoesters as Multi-Target Compounds against Resistant Cancers JF - CANCERS J2 - CANCERS VL - 13 PY - 2021 IS - 18 PG - 26 SN - 2072-6694 DO - 10.3390/cancers13184563 UR - https://m2.mtmt.hu/api/publication/32201163 ID - 32201163 N1 - Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Faculty of Medicine, University of Szeged, Semmelweis utca 6, Szeged, 6725, Hungary Department of Biochemistry and Microbiology, Faculty of Food and Biochemical Technology, University of Chemistry and Technology Prague, Technická 3, Prague 6166 28, Czech Republic Instituto de Química Orgánica General (IQOG-CSIC), Consejo Superior de Investigaciones Científicas, Juan de la Cierva 3, Madrid, 28006, Spain Cited By :7 Export Date: 8 February 2023 Correspondence Address: Viktorová, J.; Department of Biochemistry and Microbiology, Technická 3, Prague 6, Czech Republic; email: prokesoj@vscht.cz Correspondence Address: Spengler, G.; Department of Medical Microbiology, Semmelweis utca 6, Hungary; email: spengler.gabriella@med.u-szeged.hu Correspondence Address: Domínguez-Álvarez, E.; Instituto de Química Orgánica General (IQOG-CSIC), Juan de la Cierva 3, Spain; email: e.dominguez-alvarez@iqog.csic.es Chemicals/CAS: adenosine triphosphatase, 37289-25-1, 9000-83-3 Funding details: LTC19007 Funding details: GINOP-2.3.2-15-2016-00038 Funding details: European Cooperation in Science and Technology, COST Funding details: Consejo Superior de Investigaciones Científicas, CSIC, 22010090, LINKA20285 Funding text 1: Funding: The study was supported by the projects SZTE ÁOK-KKA 2018/270-62-2 of the University of Szeged, Faculty of Medicine and GINOP-2.3.2-15-2016-00038 (Hungary); and Consejo Superior de Investigaciones Científicas (CSIC, Spain, project LINKA20285). This research was funded by VISEGRAD FUND, grant number 22010090; and by the mobility project from the Czech Ministry of Education, Youth and Sports INTER-COST, grant number LTC19007. The study was supported by COST Action 17104 New Diagnostic and Therapeutic Tools Against Multidrug Resistant Tumours (STRATAGEM). The study was supported also by two cultural associations: “Trevinca” and “Iniciativas Ropelanas”. LA - English DB - MTMT ER - TY - JOUR AU - van Geldermalsen, M. AU - Wang, Q. AU - Nagarajah, R. AU - Marshall, A. D. AU - Thoeng, A. AU - Gao, D. AU - Ritchie, W. AU - Feng, Y. AU - Bailey, C. G. AU - Deng, N. AU - Harvey, K. AU - Beith, J. M. AU - Selinger, C. I. AU - O'Toole, S. A. AU - Rasko, John AU - Holst, J. TI - ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer JF - ONCOGENE J2 - ONCOGENE VL - 35 PY - 2016 IS - 24 SP - 3201 EP - 3208 PG - 8 SN - 0950-9232 DO - 10.1038/onc.2015.381 UR - https://m2.mtmt.hu/api/publication/35236916 ID - 35236916 N1 - Origins of Cancer Program, Centenary Institute, Camperdown, 2042, NSW, Australia Gene and Stem Cell Therapy Program, Centenary Institute, Camperdown, NSW, Australia Sydney Medical School, University of Sydney, Sydney, NSW, Australia Bioinformatics Laboratory, Centenary Institute, Camperdown, NSW, Australia Kinghorn Cancer Centre, Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia Department of Medical Oncology, Chris o'Brien Lifehouse, Camperdown, NSW, Australia Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney, NSW, Australia Export Date: 17 October 2024; Cited By: 438; Correspondence Address: J. Holst; Origins of Cancer Program, Centenary Institute, Camperdown, 2042, Australia; email: j.holst@centenary.org.au; CODEN: ONCNE LA - English DB - MTMT ER - TY - JOUR AU - Chang-Claude, J AU - Andrieu, N AU - Rookus, M AU - Brohet, R AU - Antoniou, AC AU - Peock, S AU - Davidson, R AU - Izatt, L AU - Cole, T AU - Nogue`s C, . AU - Luporsi, E AU - Huiart, L AU - Hoogerbrugge, N AU - Van, Leeuwen FE AU - Osorio, A AU - Eyfjord, J AU - Radice, P AU - Goldgar, DE AU - Easton, DF ED - Epidemiological, Study of Familial Breast Cancer (EMBRACE) / Collaborative Organization ED - Gene, Etude Prospective Sein Ovaire (GENEPSO) / Collaborative Organization ED - Genen, Omgeving studie van de werkgroep Hereditiair Borstkanker Onderzoek Nederland (GEO-HEBON) / Collaborative Organization AU - Oláh, Edit ED - International, BRCA1/2 Carrier Cohort Study (IBCCS) collaborators group / Collaborative Organization TI - Age at Menarche and Menopause and Breast Cancer Risk in the International BRCA1/2 Carrier Cohort Study JF - CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION J2 - CANCER EPIDEM BIOMAR VL - 16 PY - 2007 IS - 4 SP - 740 EP - 746 PG - 7 SN - 1055-9965 DO - 10.1158/1055-9965.EPI-06-0829 UR - https://m2.mtmt.hu/api/publication/2460237 ID - 2460237 N1 - Funding Agency and Grant Number: NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA081203] Funding Source: NIH RePORTER; NCI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA81203] Funding Source: Medline LA - English DB - MTMT ER - TY - JOUR AU - Szakács, Gergely AU - Paterson, JK AU - Ludwig, JA AU - Booth-Genthe, C AU - Gottesman, MM TI - Targeting multidrug resistance in cancer JF - NATURE REVIEWS DRUG DISCOVERY J2 - NAT REV DRUG DISCOV VL - 5 PY - 2006 IS - 3 SP - 219 EP - 234 PG - 16 SN - 1474-1776 DO - 10.1038/nrd1984 UR - https://m2.mtmt.hu/api/publication/151634 ID - 151634 LA - English DB - MTMT ER -