Cytotoxicity and cytoprotective activity in naphthalenediols depends on their tendency to form naphthoquinones
We consider the cytotoxicity and the protection against oxidative stress for members of the naphthalenediol family and the known antioxidant epigallocatechin gallate (EGCG). Compounds include the 1,2-naphthalenediol (1,2-ND), 1,4-ND, 2,3-ND, 1,8-ND, and 1,4-dipropyl-2,3-naphthalenediol (DPND). The cell line is an adherent clone of rat pheochromocytoma (PC12-AC). Oxidative stress was induced by the peroxyl radical generator AAPH. The relative order of cytotoxicity was 1,4-ND > 1,2-ND > DPND > 2,3-ND > 1,8-ND > EGCG, with EC50's of 15, 40, 160, >250, >250, >>250 μM, respectively. Despite their high toxicity, both 1,4-ND and 1,2-ND showed narrow zones of protective behavior whereas DPND, 2,3-ND and 1,8-ND and especially EGCG showed an extended protective range. The total protection obtained for the combination of cells/oxidative stressor/protective compounds (PC12-AC/AAPH/naphthalenediols) was defined by an integrated measure, the cytoprotective area (CPA). We relate the observed cytotoxicity and CPA to the different electronic structures of the naphthalenediols, characterized by the first and second bond dissociation enthalpies and the pKa's for parent (diol) and semiquinone. Since the 2,3- and 1,8-naphthalenediols do not form quinones, their cytotoxicity is much lower than for the compounds which do. Thus selected members of the naphthalenediol family show promise as antioxidants.
|Keywords||Antioxidant activity, Bond dissociation enthalpy, Free radicals, Naphthalenediol (naphthohydroquinone) cytotoxicity, PC12 adrenal pheochromocytoma cells, Quinone redox cycling|
|Journal||Free Radical Biology and Medicine|
Flueraru, M. (Mihaela), Chichirau, A. (Alexandru), Chepelev, L.L. (Leonid L.), Willmore, W, Durst, T. (Tony), Charron, M. (Martin), … Wright, J.S. (2005). Cytotoxicity and cytoprotective activity in naphthalenediols depends on their tendency to form naphthoquinones. Free Radical Biology and Medicine, 39(10), 1368–1377. doi:10.1016/j.freeradbiomed.2005.06.020