Total Synthesis of Dendroamide A, a Novel Cyclic Peptide That Reverses Multiple Drug Resistance

2001 ◽  
Vol 66 (10) ◽  
pp. 3459-3466 ◽  
Author(s):  
Zuping Xia ◽  
Charles D. Smith
Keyword(s):  
Drug Resistance ◽  
Total Synthesis ◽  
Cyclic Peptide ◽  
Multiple Drug Resistance ◽  
Multiple Drug

scholarly journals (+)-Discodermolide: A Marine Natural Product Against Cancer

2004 ◽  
Vol 4 ◽  
pp. 415-436 ◽  
Author(s):  
Marcus Viníus Nora De Souza
Keyword(s):  
Drug Resistance ◽  
Total Synthesis ◽  
Natural Product ◽  
Multiple Drug Resistance ◽  
Marine Natural Product ◽  
Cellular Biology ◽  
Cancer Drug ◽  
Multiple Drug ◽  
Important Target ◽  
Nanomolar Range

(+)-Discodermolide was isolated in 1990 by Gunasekera et al. from the deep-water Caribbean sponge Discodermia dissoluta. It attacks cancer cells in a similar way to the successful cancer drug Taxol® that has become the best-selling anticancer drug in history. Taxol is also the first natural product described that stabilizes the microtubules involved in many aspects of cellular biology and that represent an important target of anticancer chemotherapeutics. However, (+)-discodermolide appears to be far more potent than Taxol® against tumors that have developed multiple-drug resistance, with an IC50in the low nanomolar range. Due to these excellent results, this natural product was licensed to Novartis Pharmaceutical Corporation in early 1998. The present review covers the history, biological activity, total synthesis, and synthetic analogs of (+)-discodermolide.

Do Multiple Drug Resistance Transporters Interfere with Cell Functioning under Normal Conditions?

2020 ◽  
Vol 85 (12-13) ◽  
pp. 1560-1569
Author(s):  
D. A. Knorre ◽  
K. V. Galkina ◽  
T. Shirokovskikh ◽  
A. Banerjee ◽  
R. Prasad
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Multiple Drug

scholarly journals Amelioration of the Cost of Conjugative Plasmid Carriage in Eschericha coli K12

Genetics ◽  
2003 ◽  
Vol 165 (4) ◽  
pp. 1641-1649
Author(s):  
Cecilia Dahlberg ◽  
Lin Chao
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Conjugative Plasmid ◽  
Energetic Cost ◽  
Multiple Drug ◽  
Genetic Changes ◽  
Batch Cultures ◽  
Transfer Rates ◽  
Bacterial Plasmid ◽  
The Cost

Abstract Although plasmids can provide beneficial functions to their host bacteria, they might confer a physiological or energetic cost. This study examines how natural selection may reduce the cost of carrying conjugative plasmids with drug-resistance markers in the absence of antibiotic selection. We studied two plasmids, R1 and RP4, both of which carry multiple drug resistance genes and were shown to impose an initial fitness cost on Escherichia coli. To determine if and how the cost could be reduced, we subjected plasmid-containing bacteria to 1100 generations of evolution in batch cultures. Analysis of the evolved populations revealed that plasmid loss never occurred, but that the cost was reduced through genetic changes in both the plasmids and the bacteria. Changes in the plasmids were inferred by the demonstration that evolved plasmids no longer imposed a cost on their hosts when transferred to a plasmid-free clone of the ancestral E. coli. Changes in the bacteria were shown by the lowered cost when the ancestral plasmids were introduced into evolved bacteria that had been cured of their (evolved) plasmids. Additionally, changes in the bacteria were inferred because conjugative transfer rates of evolved R1 plasmids were lower in the evolved host than in the ancestral host. Our results suggest that once a conjugative bacterial plasmid has invaded a bacterial population it will remain even if the original selection is discontinued.

Sign in / Sign up

Export Citation Format

Share Document