Abstract
Veskamide, enferamide, becatamide, and oretamide are phenolic amides whose analogues are found in plants. In this study, the four amides were prepared by chemical synthesis and their protective effects on H(2)O(2)-induced apoptosis in PC-12 cells were investigated. The syntheses were relatively simple and the yields were more than 43%. Using NMR spectroscopic methods, the chemical structures of veskamide, enferamide, becatamide, and oretamide were confirmed. The decreasing order of the protective effects on H(2)O(2)-induced apoptosis was becatamide>enferamide≥oretamide>veskamide. In fact, becatamide suppressed H(2)O(2)-induced mitochondrial membrane depolarization in a dose-dependent manner. At the concentration of 10 μM, becatamide maintained mitochondrial membrane depolarization at 16% compared to 51% in H(2)O(2)-treated PC-12 cells (P<0.05). Also, at the same concentration, becatamide inhibited H(2)O(2)-induced caspase-9 activation and caspase-independent chromatin condensation by 68% (P<0.05) and 73% (P<0.05), respectively. This is the first report about the chemical synthesis of becatamide and its potential biological activity to inhibit H(2)O(2)-induced apoptosis of PC-12 cells via protecting mitochondrial membrane integrity, thereby suppressing caspase-9 activation and chromatin condensation.