Synthesis and antioxidative activity of metalloporphyrins bearing 2,6-di-tert-butylphenol pendants.
The novel metalloporphyrins (M=HH, Fe, Mn, Co, Cu, Zn) bearing 2,6-di-tert-butylphenol pendants as antioxidant substituents, and a long chain hydrocarbon palmitoyl group have been synthesized. The oxidation of compounds by PbO2 leads to the formation of the corresponding 2,6-di-tert-butylphenoxyl radicals studied by EPR. The activity of porphyrins in lipid peroxidation has been examined using (1) in vitro lipid peroxidation induced by tert-butylhydroperoxide in respiring rat liver mitochondria, (2) in vitro lipid peroxidation in liver homogenates of Wistar strain rats, and (3) a model process of peroxidation of (Z)-octadec-9-enic (oleic) acid as a structural fragment of lipids. The activity of these compounds depends dramatically on the nature of metal and might be changed from antioxidative (M=HH, Mn, Cu, Zn) to indifferent (M=Co), and to pro-oxidative one (M=Fe). The anti- or pro-oxidative action of these compounds may be derived from the concurrence between the involvement of 2,6-di-tert-butylphenol pendants acting as radical scavengers and redox active metal center promoting oxidation processes. The results of this study suggest that the polytopic compounds combining in one molecule 2,6-di-tert-butylphenol pendants, metalloporphyrin moiety, and a palmitoyl group, are membrane active compounds and might be studied in an effort to find novel pharmaceutical agents.
Milaeva
E R
ER
Organic Chemistry Department, Moscow State Lomonosov University, 119992 Moscow, Russian Federation. milaeva@org.chem.msu.ru
Gerasimova
O A
OA
Jingwei
Zhang
Z
Shpakovsky
D B
DB
Syrbu
S A
SA
Semeykin
A S
AS
Koifman
O I
OI
Kireeva
E G
EG
Shevtsova
E F
EF
Bachurin
S O
SO
Zefirov
N S
NS
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology*; D003035:Cobalt / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D007501:Iron / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008345:Manganese / Q000737:chemistry; D008665:Metalloporphyrins / Q000138:chemical synthesis* / Q000494:pharmacology*; D051336:Mitochondrial Membranes / Q000187:drug effects; D019301:Oleic Acid / Q000737:chemistry; D010169:Palmitic Acids / Q000737:chemistry* / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000737:chemistry
D000975:Antioxidants; D008665:Metalloporphyrins; D010169:Palmitic Acids; D010636:Phenols; C035407:2,6-di-tert-butylphenol; D019301:Oleic Acid; D003035:Cobalt; D008345:Manganese; D003300:Copper; D007501:Iron; D015032:Zinc