High lipophilicity of meta Mn(III) N-alkylpyridylporphyrin-based superoxide dismutase mimics compensates for their lower antioxidant potency and makes them as effective as ortho analogues in protecting superoxide dismutase-deficient Escherichia coli.
Lipophilicity/bioavailibility of Mn(III) N-alkylpyridylporphyrin-based superoxide dismutase (SOD) mimics has a major impact on their in vivo ability to suppress oxidative stress. Meta isomers are less potent SOD mimics than ortho analogues but are 10-fold more lipophilic and more planar. Enhanced lipophilicity contributes to their higher accumulation in cytosol of SOD-deficient Escherichia coli, compensating for their lower potency; consequently, both isomers exert similar-to-identical protection of SOD-deficient E. coli. Thus meta isomers may be prospective therapeutics as are ortho porphyrins.
Kos
Ivan
I
Department of Radiation Oncology, Duke University Medical School, Durham, North Carolina 27710, USA.
Benov
Ludmil
L
Spasojević
Ivan
I
Rebouças
Júlio S
JS
Batinić-Haberle
Ines
I
D000332:Aerobiosis; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*; D057927:Hydrophobic and Hydrophilic Interactions; D007536:Isomerism; D008345:Manganese / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011166:Porphyrins / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000378:metabolism
D000975:Antioxidants; D009942:Organometallic Compounds; D011166:Porphyrins; D008345:Manganese; D013482:Superoxide Dismutase