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Activity‐Guided Isolation of a Sirtuin2 Inhibiting Compound from Coffee: Structural and Activity Confirmation of Javamide‐II ( N ‐caffeoyltryptophan) and its Cellular Effects on Histone H3, Alpha‐Tubulin and p53 Implicated in Human Diseases.
Author(s) -
Park Jae
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.118.2
Subject(s) - enzyme , chemistry , high performance liquid chromatography , biochemistry , amide , inhibitory postsynaptic potential , tubulin , lead compound , alpha (finance) , stereochemistry , biology , in vitro , chromatography , medicine , microtubule , microbiology and biotechnology , neuroscience , construct validity , nursing , patient satisfaction
Coffee is one of most consumed drinks worldwide with potential health effects on several chronic diseases including neuronal diseases. Interestingly, recent studies suggest that the inhibition of sirtuin2 may be beneficial in restoring cognition in Alzheimer's disease. Therefore, in this paper, potential sirtuin2 inhibitors were screened using several coffee samples. For this study, a HPLC method was developed and coffee samples were fractionated by the HPLC method. Then, the fractions were screened using a sirtuin2 inhibition assay. The screening led to the isolation of a potent sirtuin2 inhibitory compound from the fraction with the highest inhibition activity. Using HPLC and NMR spectroscopic techniques, the chemical structure of the compound was determined as Javamide‐II ( N ‐caffeoyltryptophan). Javamide‐II was a potent sirtuin2 inhibitor inhibiting the enzymes by 39% at the concentration of 1 microM ( P < 0.05). To confirm that Javamide‐IIis the compound able to inhibit sirtuin2, the amide was chemically synthesized and its capability of inhibiting sirtuin2 was evaluated. Both isolated and synthesized N‐caffeoyltryptophan exhibited very similar pattern of sirtuin2 inhibition with identical IC 50 and K i values, suggesting that Javamide‐II may be the compound able to inhibit sirtuin2. In this paper, we also report potential effects of Javamide‐II and its analogues on histone H3, alpha‐tubulin and p53 in cellular levels, suggesting that Javamide‐II and analogues found in coffee are potent sirtuin2 inhibitors with potential uses on several human diseases.