scholarly journals Synthesis of 5-oxyquinoline derivatives for reversal of multidrug resistance

2012 ◽  
Vol 8 ◽  
pp. 1700-1704 ◽  
Author(s):  
Torsten Dittrich ◽  
Nils Hanekop ◽  
Nacera Infed ◽  
Lutz Schmitt ◽  
Manfred Braun
Keyword(s):  
Multidrug Resistance ◽  
Abc Transporter ◽  
Efflux Pumps ◽  
Lead Compound ◽  
Transport Activity ◽  
Multidrug Efflux ◽  
P Glycoprotein ◽  
Multidrug Efflux Pumps ◽  
Atp Binding Cassette Transporters ◽  
Inhibitory Power

The inhibition of ABC (ATP binding cassette) transporters is considered a powerful tool to reverse multidrug resistance. Zosuquidar featuring a difluorocyclopropyl-annulated dibenzosuberyl moiety has been found to be an inhibitor of the P-glycoprotein, one of the best-studied multidrug efflux pumps. Twelve 5-oxyisoquinoline derivatives, which are analogues of zosuquidar wherein the dibenzosuberyl-piperazine moiety is replaced by either a diarylaminopiperidine or a piperidone-derived acetal or thioacetal group, have been synthesized as pure enantiomers. Their inhibitory power has been evaluated for the bacterial multidrug-resistance ABC transporter LmrCD and fungal Pdr5. Four of the newly synthesized compounds reduced the transport activity to a higher degree than zosuquidar, being up to fourfold more efficient than the lead compound in the case of LmrCD and about two times better for Pdr5.

scholarly journals In silico studies of aminated thioxanthones: bacterial multidrug efflux pumps vs P-glycoprotein

2018 ◽  
Author(s):  
Emília Sousa ◽  
Fernando Durães ◽  
Andreia Palmeira ◽  
Madalena Pinto
Keyword(s):  
In Silico ◽  
Efflux Pumps ◽  
Multidrug Efflux ◽  
P Glycoprotein ◽  
Multidrug Efflux Pumps

scholarly journals Overcoming Multidrug Resistance: Flavonoid and Terpenoid Nitrogen-Containing Derivatives as ABC Transporter Modulators

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3364 ◽  
Author(s):  
Bruno M. F. Gonçalves ◽  
David S. P. Cardoso ◽  
Maria-José U. Ferreira
Keyword(s):  
Multidrug Resistance ◽  
Natural Product ◽  
Abc Transporter ◽  
Efflux Pumps ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
Multidrug Resistance Protein 1 ◽  
P Glycoprotein ◽  
Resistance Protein

Multidrug resistance (MDR) in cancer is one of the main limitations for chemotherapy success. Numerous mechanisms are behind the MDR phenomenon wherein the overexpression of the ATP-binding cassette (ABC) transporter proteins P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance protein 1 (MRP1) is highlighted as a prime factor. Natural product-derived compounds are being addressed as promising ABC transporter modulators to tackle MDR. Flavonoids and terpenoids have been extensively explored in this field as mono or dual modulators of these efflux pumps. Nitrogen-bearing moieties on these scaffolds were proved to influence the modulation of ABC transporters efflux function. This review highlights the potential of semisynthetic nitrogen-containing flavonoid and terpenoid derivatives as candidates for the design of effective MDR reversers. A brief introduction concerning the major role of efflux pumps in multidrug resistance, the potential of natural product-derived compounds in MDR reversal, namely natural flavonoid and terpenoids, and the effect of the introduction of nitrogen-containing groups are provided. The main modifications that have been performed during last few years to generate flavonoid and terpenoid derivatives, bearing nitrogen moieties, such as aliphatic, aromatic and heterocycle amine, amide, and related functional groups, as well as their P-gp, MRP1 and BCRP inhibitory activities are reviewed and discussed.

scholarly journals Molecular Cloning and Characterization of an ABC Multidrug Efflux Pump, VcaM, in Non-O1 Vibrio cholerae

2003 ◽  
Vol 47 (8) ◽  
pp. 2413-2417 ◽  
Author(s):  
Nazmul Huda ◽  
Eun-Woo Lee ◽  
Jing Chen ◽  
Yuji Morita ◽  
Teruo Kuroda ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Vibrio Cholerae ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Atp Binding ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Hoechst 33342 ◽  
Hydrophobic Domain ◽  
Multidrug Efflux Pumps

ABSTRACT A gene responsible for multidrug resistance was cloned from the chromosomal DNA of non-O1 Vibrio cholerae NCTC 4716 by using as a host drug-hypersensitive Escherichia coli strain KAM32, which lacks major multidrug efflux pumps. E. coli cells transformed with the gene showed elevated levels of resistance to a number of structurally dissimilar drugs, such as tetracycline, norfloxacin, ciprofloxacin, doxorubicin, daunomycin, 4′,6-diamidino-2-phenylindole, and Hoechst 33342. We determined the nucleotide sequence and found one open reading frame. We designated the gene vcaM. The deduced product, VcaM, seems to be a polypeptide with 619 amino acid residues (69 kDa) that has a putative topology of six transmembrane segments in the N-terminal hydrophobic domain, followed by an ATP binding domain in the C-terminal hydrophilic region. The sequence of VcaM was shown to be similar to those of human multidrug resistance proteins P-glycoprotein MDR1 and lactococcal LmrA, which are driven by ATP. The efflux of Hoechst 33342 and doxorubicin from cells possessing VcaM was detected. The efflux activity was inhibited by reserpine and sodium o-vanadate, which are potent inhibitors of MDR1 and LmrA. Thus, we conclude that VcaM is a member of the family of multidrug efflux pumps of the ATP binding cassette type and the first experimentally proven example of a multidrug efflux pump of this family in gram-negative bacteria.

Inhibitors of bacterial multidrug efflux pumps from the resin glycosides of Ipomoea species

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
R Pereda-Miranda ◽  
L Chérigo ◽  
M Fragoso-Serrano ◽  
N Jacobo-Herrera ◽  
GW Kaatz ◽  
...  
Keyword(s):  
Efflux Pumps ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pumps ◽  
Ipomoea Species

Involvement of the Multidrug Efflux Pumps in Betalactams Resistant Pseudomonas aerugionsa Clinical Isolates Collected from Burn Patients in Iran

2016 ◽  
Vol 16 (3) ◽  
pp. 172-177 ◽  
Author(s):  
Aslan Bijari ◽  
Leila Azimi ◽  
Fatemeh Fallah ◽  
Abdollah Ardebili ◽  
Elnaz Lari ◽  
...  
Keyword(s):  
Efflux Pumps ◽  
Clinical Isolates ◽  
Burn Patients ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pumps

scholarly journals Multidrug Efflux Pumps and the Two-Faced Janus of Substrates and Inhibitors

2021 ◽  
Vol 54 (4) ◽  
pp. 930-939
Author(s):  
Helen I. Zgurskaya ◽  
John K. Walker ◽  
Jerry M. Parks ◽  
Valentin V. Rybenkov
Keyword(s):  
Efflux Pumps ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pumps
Sign in / Sign up

Export Citation Format

Share Document