Reversal of multidrug resistance by amphiphilic morning glory resin glycosides in bacterial pathogens and human cancer cells

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.

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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

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Acknowledgements

The studies reviewed in this manuscript were supported by grants from CONACyT (CB101380, CB220535) and DGAPA-UNAM (PAPIIT IN212813; IN215016; IN208019). The authors are grateful to Dr Mabel Fragoso-Serrano, and all the graduate students, postdoctoral researchers, and collaborators cited in the references for their significant contributions to this investigation. The authors thank Mr Morris Thompson for essay editing and proofreading of the manuscript. Based on the PhD thesis of coauthor J. Lira-Ricárdez (Posgrado en Ciencias Químicas, UNAM).

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Correspondence to Rogelio Pereda-Miranda.

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Lira-Ricárdez, J., Pereda-Miranda, R. Reversal of multidrug resistance by amphiphilic morning glory resin glycosides in bacterial pathogens and human cancer cells. Phytochem Rev 19, 1211–1229 (2020). https://doi.org/10.1007/s11101-019-09631-1

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Keywords

  • Acylsugar diversity
  • Amphiphilicity
  • Chemosensitizer
  • Efflux pump inhibitor
  • Multidrug-resistance