Potent antioxidant activity of a dithiocarbamate-related compound from a marine hydroid

Recently, we discovered a novel class of natural products, named the triden tatols, in a marine hydroid. Close examination of their molecular structure s suggested that they may have antioxidant activity. This observation promp ted us to evaluate in vitro the capacity of one of these tridentatols, viz. tridentatol A, to inhibit lipid peroxidation using human low density lipop rotein (LDL) as an experimental model. LDL was incubated with 5 mu M cupric chloride (Cu2+) in the absence and presence of tridentatol A or a referenc e antioxidant standard, i.e. vitamin E. The onset of rapid formation of con jugated lipid hydroperoxides was delayed in a concentration-dependent manne r by tridentatol A. More specifically, LDL incubated with Cu2+ had a lag-ph ase time (the elapsed time before the onset of rapid formation of conjugate d lipid hydroperoxides) of 150 min. However, when 0.5 mu M tridentatol A wa s present during incubation, the lag phase time was extended to 225 min. Wi th 1 mu M tridentatol A, the lag phase time was 300 min. The same concentra tions of vitamin E produced noticeably lower lag phase times. Thus, compare d with vitamin E, tridentatol A better protected against the formation of c onjugated lipid hydroperoxides in LDL. Direct colorimetric measurements of both lipid hydroperoxides and thiobarbituric acid-reactive substances confi rmed the greater potency of tridentatol A relative to vitamin E. Furthermor e, tridentatol A negated the Cu2+ induced increase in electrophoretic mobil ity of LDL to a greater extent than vitamin E. In conclusion, tridentatol A is a powerful antioxidant against lipid peroxidation of LDL and is signifi cantly more potent than vitamin E in this regard. (C) 1999 Elsevier Science Inc.