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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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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author Phạm Văn Thoại
Nguyen Hai Nam
author_facet Phạm Văn Thoại
Nguyen Hai Nam
author_sort Phạm Văn Thoại
collection DOAJ
description 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.
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issn 2090-9063
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spelling doaj-art-9b5668250053495b84117e7ff0ee2c4a2025-08-20T03:36:58ZengWileyJournal of Chemistry2090-90632090-90712013-01-01201310.1155/2013/684760684760Design and Synthesis of Sustain-Acting Melatonin ProdrugsPhạm Văn Thoại0Nguyen Hai Nam1Department of Pharmaceutical Chemistry, Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, VietnamDepartment of Pharmaceutical Chemistry, Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, VietnamTwelve 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.http://dx.doi.org/10.1155/2013/684760
spellingShingle Phạm Văn Thoại
Nguyen Hai Nam
Design and Synthesis of Sustain-Acting Melatonin Prodrugs
Journal of Chemistry
title Design and Synthesis of Sustain-Acting Melatonin Prodrugs
title_full Design and Synthesis of Sustain-Acting Melatonin Prodrugs
title_fullStr Design and Synthesis of Sustain-Acting Melatonin Prodrugs
title_full_unstemmed Design and Synthesis of Sustain-Acting Melatonin Prodrugs
title_short Design and Synthesis of Sustain-Acting Melatonin Prodrugs
title_sort design and synthesis of sustain acting melatonin prodrugs
url http://dx.doi.org/10.1155/2013/684760
work_keys_str_mv AT phamvanthoai designandsynthesisofsustainactingmelatoninprodrugs
AT nguyenhainam designandsynthesisofsustainactingmelatoninprodrugs