L-1416, a novel MDR reversing agent with possible reduced calcium antagonism.
Pharmacol Rep
; 66(6): 1140-7, 2014 Dec.
Article
in En
| MEDLINE
| ID: mdl-25443747
ABSTRACT
BACKGROUND:
Multidrug efflux transporter P-glycoprotein (P-gp) is highly expressed on membrane of tumor cells and supposed to be implicated in the resistance to tumor chemotherapy. However, currently none of P-gp inhibitors has been approved by Food and Drug Administration not only due to toxicity but also lack of efficacy in clinical trials.METHODS:
To solve the problem, our lab synthesized a novel compound named 1416 [1-(2,6-dimethylphenoxy)-3,4-dimethoxyphenylethylamino) propane hydrochloride] with the hope of high P-gp inhibition and low side effects. Caco-2 cell monolayer and tumor bearing mice were used to evaluate the P-gp inhibition of 1416 in vitro and in vivo, respectively. One of its potential side effects, calcium antagonism was also evaluated.RESULTS:
Results showed that 1416 showed a similar P-gp inhibition as verapamil in Caco-2 cell monolayer. No significant difference was observed in antitumor enhancement when the optical isomers of 1416 (D-1416 and L-1416) were co-administered with vinblastine. In calcium antagonism, L-1416 showed less calcium inhibition than both D-1416 and verapamil.CONCLUSION:
The novel compound 1416 could significantly increase the antitumor effects of cytotoxic drugs and one of its optical isomers, L-1416, might be more promising due to its potential low calcium antagonism.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenethylamines
/
Propylamines
/
Calcium
/
ATP Binding Cassette Transporter, Subfamily B, Member 1
/
Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
Pharmacol Rep
Journal subject:
FARMACOLOGIA
Year:
2014
Document type:
Article
Affiliation country:
China