Design and Synthesis of Sustain-Acting Melatonin Prodrugs

Abstract EN

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 N1-succinyl and N1-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 N1-succinyl and N1-glutaroylmelatonin derivatives (compounds 11 and 12) could be promising as sustained release prodrugs of melatonin.