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Introduction: Melatonin (MLT) is the pineal hormone, which has many pharmacological activities as following antioxidant, anticancer, and immune enhancement. Due to its antioxidant ability, MLT was investigated the neuroprotective effect on neurons. However, the poor pharmacokinetic profiles such as bioavailability and rapid metabolism were its limit for pharmacological study. Therefore, the structure development is needed for improving pharmacological activity. Materials and Method: N-acetyl melatonin (AcO-MLT) was produced from the reaction of MLT and acetic anhydride by using 4,4-dimethyl aminopyridine (DMAP) as catalyst. After the reaction completed, liquid-liquid extraction and chromatographic purification were used to obtain AcO-MLT. Then, MLT and N-acetyl melatonin AcO-MLT were evaluated neuroprotective ability by serum deprivation method and neuritogenic effect in P19-derived neurons. Cell viability was measured by XTT reduction assay. Results: Both of MLT and its derivative, AcO-MLT, at 1 nM significantly protected neuron cells from toxicity of oxidative stress. From XTT reduction assay showed cell viability treated with MLT and AcO-MLT compared with oxidative stress condition group was 98.0% ± 44.3, 74.3% ± 7.4, and 15.7% ± 5.2, respectively. MLT and AcO-MLT also increased the number of neurites compared with the control (3.4 ± 1.1, 4.0 ± 1.7, and 2.0 ± 1.1, respectively). Conclusion: MLT and AcO-MLT significantly protected neuronal cell death from oxidative stress. For neuritogenic ability, MLT and AcO-MLT could promote the neurite outgrowth but could not increase the neurite length. From the result can be summarized that MLT and its N-acetylated derivative may have potential to further study and develop as a neuroprotective agent
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