Studies of Synthetic Catechin Analogues Useful for Antioxidant Therapy

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The protective role of antioxidants against free-radical associated diseases has been widely studied and this has prompted the development of new types of antioxidants. A planar catechin analogue (1H_2), in which catechol and chroman moieties in catechin were constrained to be planar, was synthesized via oxa-Pictet Spengler reaction using catechin and aceton with BF_3.Et_2O. The radical-scavenging activities of 1H_2 were examined using galvinoxyl radical (G^・), a stable oxygen-centered radical, showing that the hydrogen transfer reaction from 1H_2 to G^・ is 5-fold faster than that of hydrogen transfer from the native catechin to G^・. The kinetics of hydrogen transfer from catechins to cumylperoxyl radical was also examined in propionitrile (EtCN) at low temperature with use of ESR, showing that the rate of hydrogen transfer from P1H_2 is significantly faster than that from catechin. Under basic conditions, the dianion (1^<2->) of 1H_2 reduced molecular oxygen to produce superoxide anion (O_2^<・->). However, the electron transfer rate was slower than that of catechin, suggesting that 1H_2 may be a promising novel antioxidant with reduced pro-oxidant activity. The 1H_2 also showed an enhanced protective effect against the oxidative DNA damage induced by Fenton reaction without the pro-oxidant effect, which is usually observed in the case of the native catechin.Finally, the planar catechin acalogue showed the strong radical scavenging ability and reduced prooxidant effect responsible for the less-efficient generation of O_2^<・->. The completed inhibition of DNA strand scission is also expected the efficient protection toward oxidative damage of biopolymers caused by the reactive oxygen species. The lipophilic property of 1H_2 is also useful for suppressing free-radical associated event, especially in the cell membrane. Therefore, 1H_2 might be very effective for the prevention and/or treatment of free radical-associated diseases.