Design and Synthesis of Sustain-Acting Melatonin Prodrugs

Twelve melatonin amide prodrugs aiming at prolonging the action of melatonin in vivo by improving its half-life were designed and synthesized. Using an 80% human plasma model, it was found that the aliphatic amide derivatives were relatively stable and melatonin release from these compounds was not...

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Bibliographic Details
Main Authors: Phạm Văn Thoại, Nguyen Hai Nam
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Journal of Chemistry
Online Access:http://dx.doi.org/10.1155/2013/684760
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Summary:Twelve melatonin amide prodrugs aiming at prolonging the action of melatonin in vivo by improving its half-life were designed and synthesized. Using an 80% human plasma model, it was found that the aliphatic amide derivatives were relatively stable and melatonin release from these compounds was not sufficient with melatonin release percentage. After 4-hour incubation with 80% human plasma, the melatonin release percentage achieved only approximately less than 20%. In contrast, the -succinyl and -glutaroylmelatonin derivatives (compounds 11 and 12, resp.) were found to release melatonin in much higher rates. After 3-hour incubation in 80% human plasma, the melatonin release rates from 11 and 12 were found to be 67.3 and 75.6%, respectively. From these results, the -succinyl and -glutaroylmelatonin derivatives (compounds 11 and 12) could be promising as sustained release prodrugs of melatonin.
ISSN:2090-9063
2090-9071