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Publication
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| Title of Article |
In Silico ADME and Metabolism Predictions and Hydrolysis Study of Melatonin Derivatives |
| Date of Acceptance |
9 November 2020 |
| Journal |
| Title of Journal |
International Journal of Tryptophan Research |
| Standard |
SCOPUS |
| Institute of Journal |
SAGE Journals |
| ISBN/ISSN |
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| Volume |
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| Issue |
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| Month |
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| Year of Publication |
2020 |
| Page |
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| Abstract |
Melatonin (MLT) is a well-known pineal hormone possessed with remarkable biological activities. However, its low oral bioavailability and high first-pass metabolism rate are important pharmacokinetics problems. Therefore, five MLT derivatives (1-5) were designed and synthesized in our group to solve these problems. In this work, in silico analysis of all synthetic derivatives for pharmacokinetic and drug-likeness parameters were predicted by SwissADME software. The results revealed that all derivatives (1-5) met the requirements for ideal oral bioavailability and CNS drugs. The molecular docking showed that the acetyl-MLT derivative (1) and the un-substitution at N1-position derivative 5 would be substrates of CYP1A2, while the lipophilic substituted N1-position derivatives 2-4 could not be metabolised by CYP1A2. Moreover, all N-amide derivatives (1-4) were hydrolysed and released less than 2.33 %MLT after 4-hour incubation in 80% human plasma. It seemed that these derivatives preferred to behave like drugs rather than prodrugs of MLT. These findings confirmed that the addition of bulky groups at the N1-position of the MLT core could prolong the half-life, increase drug absorption and penetrate the blood brain barrier into the CNS. |
| Keyword |
Melatonin, N-amide derivative, metabolism, ADME, molecular docking |
| Author |
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| Reviewing Status |
มีผู้ประเมินอิสระ |
| Status |
ได้รับการตอบรับให้ตีพิมพ์ |
| Level of Publication |
นานาชาติ |
| citation |
true |
| Part of thesis |
true |
| Attach file |
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| Citation |
0
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Journal Publication
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