Defying Multidrug Resistance! Modulation of Related Transporters by Flavonoids and Flavonolignans.

Abstract

Multidrug resistance (MDR) is a major challenge for the 21th century in both cancer chemotherapy and antibiotic treatment of bacterial infections. Efflux pumps and transport proteins play an important role in MDR. Compounds displaying inhibitory activity toward these proteins are prospective for adjuvant treatment of such conditions. Natural low-cost and nontoxic flavonoids, thanks to their vast structural diversity, offer a great pool of lead structures with broad possibility of chemical derivatizations. Various flavonoids were found to reverse both antineoplastic and bacterial multidrug resistance by inhibiting Adenosine triphosphate Binding Cassette (ABC)-transporters (human P-glycoprotein, multidrug resistance-associated protein MRP-1, breast cancer resistance protein, and bacterial ABC transporters), as well as other bacterial drug efflux pumps: major facilitator superfamily (MFS), multidrug and toxic compound extrusion (MATE), small multidrug resistance (SMR) and resistance-nodulation-cell-division (RND) transporters, and glucose transporters. Flavonoids and particularly flavonolignans are therefore highly prospective compounds for defying multidrug resistance.

• Authors: Christopher S Chambers, Jitka Viktorová, Kateřina Řehořová, David Biedermann, Lucie Turková, Tomáš Macek, Vladimír Křen, Kateřina Valentová
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 68 Issue 7 Pg. 1763-1779 (Feb 19 2020) ISSN: 1520-5118 [Electronic] United States
• PMID: 30907588 (Publication Type: Journal Article, Review)

Chemical References

• ATP-Binding Cassette Transporters
• Anti-Bacterial Agents
• Antineoplastic Agents
• Bacterial Proteins
• Flavonoids
• Flavonolignans

Topics

• ATP-Binding Cassette Transporters (antagonists & inhibitors, genetics, metabolism)
• Animals
• Anti-Bacterial Agents (pharmacology)
• Antineoplastic Agents (therapeutic use)
• Bacteria (genetics, metabolism)
• Bacterial Infections (drug therapy, microbiology)
• Bacterial Proteins (antagonists & inhibitors, genetics, metabolism)
• Drug Resistance, Bacterial
• Drug Resistance, Neoplasm
• Flavonoids (administration & dosage)
• Flavonolignans (administration & dosage)
• Humans
• Neoplasms (drug therapy, genetics, metabolism)