Antioxidant activity of the pyridoindole stobadine. Pulse radiolytic characterization of one-electron-oxidized stobadine and quenching of singlet molecular oxygen

Abstract

Antioxidant properties of stobadine, a pyridoindole derivative described to exhibit cardioprotective properties, were characterized. The radical scavenging potential of stobadine was evaluated using pulse radiolysis with optical detection, by which it is shown that one-electron oxidation of stobadine with radicals such as C6H5O., CCl3O2., Br2.-, and HO. (reaction rate constants approximately 5 x 10(8)-10(10) M-1 s-1) leads to the radical cation (absorbance maxima at 280 and 445 nm) which deprotonates from the indolic nitrogen (pKa = 5.0) to give a nitrogen-centered radical (absorbance maxima at 275, 335, and 410 nm), probably bearing a positive charge at the pyrido nitrogen. The radical of stobadine reacts with Trolox (i.e., 6-hydroxy-2,5,7,8-tetramethyl-chromane-2-carboxylic acid) with a rate constant of 1.2 x 10(7) M-1 s-1 at pH 7.0 by one-electron oxidation to yield the phenoxyl-type radical of Trolox. This reaction is reversible (k = 2 x 10(5) M-1 s-1). The redox potential of stobadine at pH 7 is 0.58 V/NHE. Stobadine is also a quencher of singlet molecular oxygen (1O2) with an overall quenching rate constant of 1.3 x 10(8) M-1 s-1, determined with the endoperoxide of 3,3'-(1,4-naphthylene)dipropionate (NDPO2) as 1O2 source and by monitoring 1O2 photoemission with a germanium diode.

Stobadine – An Indole Type Alternative to the Phenolic Antioxidant Reference Trolox

“…1B). It was demonstrated that one-electron oxidation of stobadine leads to the formation of its radical cation (Steenken et al, 1992). That deprotonates from the indolic nitrogen and gives a resonance stabilised nitrogen-centred radical.…”

“…< 5x10 6 6.6 x 10 8 (Steenken et al, 1992) 2.5 x 10 6 3.7 x 10 8 (Simic, 1980;Davies et al, 1988) DPPH . 4.9 x 10 2 (Rackova et al, 2004) 1.6 x 10 3 (Rackova et al, 2004) C 6 H 6 O .…”

“…4.9 x 10 2 (Rackova et al, 2004) 1.6 x 10 3 (Rackova et al, 2004) C 6 H 6 O . 5.1 x 10 8 (Steenken et al, 1992) 4.1 x 10 8 (Davies et al, 1988) O 2 .-7.5 x 10 2 (Kagan et al, 1993) 1.7 x 10 4 <0.1 (Nishikimi & Machlin, 1975;Bielski, 1982) 1 O 2 1.3 x 10 8 (Steenken et al, 1992) pH6 3.5x10 8 (Nonell et al, 1995) Table 1. Second-order rate constants of stobadine and trolox interaction with reactive oxygen species and 1,1`-diphenyl-2-picrylhydrazyl (DPPH) stable free radical.…”

“…Redox potential of stobadine (E = 0.58 V) (Steenken et al, 1992) is more positive than that of vitamin E (E = 0.48 V) (Neta & Steenken, 1982). Hence, at pH 7, the stobadine radical, formed as a consequence of stobadine free-radical-scavenging activity, may subtract proton from the trolox molecule resulting in regeneration of the parent stobadine molecule.…”

“…1A) has been found out to be an effective chain-breaking antioxidant scavenging a variety of reactive oxygen species (Kagan et al, 1993;Steenken et al, 1992;Stefek & Benes, 1991). The input of stobadine into the literary data on indole-type antioxidants comprises more than two hundred PubMed references.…”