Reversal of multidrug resistance by amphiphilic morning glory resin glycosides in bacterial pathogens and human cancer c
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Reversal of multidrug resistance by amphiphilic morning glory resin glycosides in bacterial pathogens and human cancer cells Jesu´s Lira-Rica´rdez . Rogelio Pereda-Miranda
Received: 8 February 2019 / Accepted: 6 July 2019 Ó Springer Nature B.V. 2019
Abstract Pathogens that express resistance to multiple drugs are becoming the norm, complicating treatment and increasing human morbidity. Acylsugars or resin glycosides from the morning glory family (Convolvulaceae) are amphipathic modulators of the efflux pumps responsible for the drug-resistant phenotype in prokaryotic and eukaryotic cells. These inhibitory effects could be used to overcome the acquired resistance to common anticancer or antimicrobial drugs by lowering the current effective therapeutic doses, thus decreasing toxic side-effects in refractory malignancies. Active chemosensitizers identified by in vitro screening methods have demonstrated the therapeutic potential of resin glycosides for further exploration as coadjuvants to avoid drug resistance and restore the clinical utility of chemotherapy in treating infections and cancer. To date, more than 20 resin glycosides have been documented as inhibitors or modulators of efflux pumps, mainly isolated from species of the genus Ipomoea. Resin glycosides have shown the ideal structural features associated with multidrug-resistant efflux pump substrates. An overview is given to the acylsugar diversity
and their amphiphilicity properties for bioactivity as leads of efflux pump inhibitors for drug development. Keywords Acylsugar diversity Amphiphilicity Chemosensitizer Efflux pump inhibitor Multidrugresistance Abbreviations EP Efflux pump EPI Efflux pump inhibitor EtBr Ethidium bromide IC50 Half maximal inhibitory concentration MDR Multidrug-resistant/resistance MIC Minimal inhibitory concentration NOR Norfloxacine P-gp P-glycoprotein RES Reserpine RG Resin glycoside Rh123 Rhodamin-123 VIN Vinblastine
Introduction J. Lira-Rica´rdez R. Pereda-Miranda (&) Departamento de Farmacia, Facultad de Quı´mica, and Programa de Maestrı´a y Doctorado en Ciencias Quı´mica, Universidad Nacional Auto´noma de Me´xico, Ciudad Universitaria, 04510 Mexico City, Mexico e-mail: [email protected]
Multidrug resistance (MDR) is a major obstacle in the chemotherapy of refractory malignancies. Multiple resistance mechanisms in cancer and life-threatening infections complicate treatment and increase both human morbidity and financial cost in health-care
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Phytochem Rev
systems. MDR phenotype is often the overexpression of plasma-membrane-associated translocases that extrude a wide range of structurally and functionally diverse lipophilic and amphipathic antibiotics, anticancer drugs, carcinogens, toxins, and other xenobiotics from inside the cells. This prevents drugs from exerting their cytotoxicity, by decreasing intracellular accumulation below a cell-killing threshold (Du et al. 2018). Cells are resistant when they are not susceptible to the concentration of a clinically
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