Phenolic acids and their derivatives found in nature are well-known for their potential biological activity. In this study, two amides derived from
-caffeic/ferulic acid and dopamine were synthesized ...and characterized by Fourier-transform infrared spectroscopy (FTIR), mass spectrometry, proton and carbon-13 nuclear magnetic resonance spectroscopy. The compounds were tested for the inhibition of acetylcholinesterase (AChE) from
and for antioxidant activity by scavenging 2,2-diphenyl-1-pycrylhydrazyl free radical (DPPH
) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) radical cation (ABTS
), reducing ferric ions, and ferrous ions chelation.
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-Feruloyldopamine displayed the highest inhibitory effect on AChE with half-maximal inhibitory concentration (
) values of 8.52 μM. In addition, an in silico study was done to determine the most favorable AChE cluster with the synthesized compounds. Further, these clusters were investigated for binding positions at the lowest free binding energy. Both synthesized hydroxycinnamates were found to be better antioxidants than the parent acids in in vitro tests applied.
-
-Caffeoyldopamine showed the best antioxidant activity in the three tested methods-against non-biological stable free radicals
5.95 μM for DPPH
, 0.24 μM for the ABTS
method, and for reducing power (ascorbic acid equivalent
822.45 μmol/mmol)-while for chelation activity against Fe
ions
-
-feruloyldopamine had slightly better antioxidant activity (
3.17 mM).
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In our searching for novel antioxidants from natural sources, N-trans-Caffeoyldopamine which was from natural product was found to be a potential compound for its remarkable ...antioxidant activity. Isoniazid (INH) and Rifampicin (RFP) is widely used for the treatment of Tuberculosis (TB) as the first line drugs, have been known to be potentially hepatotoxic and may lead to drug-induced liver injury.
Oxidative stress has been regarded as the major mechanism of the hepatotoxicity. Therefore, in this study, the possible protective effects of N-trans-Caffeoyldopamine was investigated in the hepatotoxicity caused by INH and RFP in rats. Results showed that serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and hepatic malondialdehyde (MDA) content were reduced dramatically, and hepatic superoxide dismutase (SOD) activity and glutathione (GSH) content were restored remarkably by N-trans-Caffeoyldopamine co-administration, as compared to the INH–RFP treated rats (p<0.01). Moreover, the histopathological damage of liver and the number of apoptotic hepatocytes were also significantly ameliorated by the treatment. It is therefore suggested that N-trans-Caffeoyldopamine can provide a definite protective effect against acute hepatic injury caused by INH and RFP in rats, which may mainly be associated with its antioxidative effect. Mechanisms studies indicated that it inhibited the lipid peroxidation through the cytochrome P450 2E1 (CYP2E1) downregulation.
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