In a previous study, the neuroprotection provided by some hindered
phenols of synthetic nature and
alpha-tocopherol in guinea-pig detrusor strips subjected to ischaemia/reperfusion-like conditions was shown to be related directly to the
antioxidant activity. The aim of the present study was to estimate the capability of three novel chimeric molecules derived by assembling known
antioxidant moieties, namely
FeAOX-6, comprising a chromanyl head and the polyisoprenyl sequence characteristic for
lycopene, FeCD-52, derived from the conjugation of
ascorbic acid and a
polyphenol moiety (FeRS-4) and FeDG-17, derived from the combination of
ascorbic acid and a chromanyl head, to confer neuroprotection in an in vitro model of guinea-pig whole urinary bladder subjected to
anoxia-glucopenia/
reperfusion injury. The
antioxidant potential of these compounds was determined by
oxygen radical absorbance capacity (ORAC) and phochemiluminescence (PCL) assays to test their peroxyl and
anion superoxide (O2(*-)) radical trapping activity, respectively.
FeAOX-6, FeCD-52 and FeDG-17 exerted both strong neuroprotective and
antioxidant activity, significantly higher than those exerted by the individual component moieties. The
antioxidant activity of FeCD-52 was 37-fold higher than that of the reference compound
trolox.
FeAOX-6 exerted remarkable neuroprotective activity, superior to that of FeCD-52 or FeDG-17, in spite of its lower
antioxidant activity. These findings indicate that assembling
antioxidant moieties yields
neuroprotective agents, the effectiveness of which, however, is not related to the
antioxidant activity. It is possible that a different partitioning in cell compartments critically involved in the oxidative damage pathway plays a role in neuroprotection exerted by these compounds.