Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 5, Issue 6, Pages 639-643Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ml400493f
Keywords
Reactive oxygen species; hydrogen peroxide; catalase activity; dinuclear Mn-porphyrin; water solubility
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Funding
- Japan Society for the promotion of Science [22300166]
- Grants-in-Aid for Scientific Research [22300166, 24650281] Funding Source: KAKEN
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Superoxide dismutase (SOD) and catalase activities of a drug are of great importance for its effective protection against reactive oxygen species (ROS)-induced injury. Achievement of catalase activity of a synthetic compound remains a challenge. Water-soluble Mn-porphyrins have high SOD and peroxynitrite (ONOO-) reducing activities, but not catalase-like activity. Herein, we are able to retain the fair SOD-like activity of a mononuclear Mn-5-(N-methylpyridinium-4-yl)-10,15,20-triphenyl porphyrin (MriM4PyP(3)P), while gaining in catalase-like activity with its dinuclear complex, 1,3-di[5-(N-methylene-pyridinium-4-yl)-10,15,20-triphenyl porphynato manganese] benzene tetrachloride (MnPD). Mechanistic study indicates that catalase-like activity of MnPD is due to synergism of two Mn active sites, where hydroxo-Mn(IV) complex is formed as an intermediate. The in vivo experiments demonstrate that MnPD significantly restores the treadmill-running ability of SOD-deficient mouse and thus indicates the therapeutic potential of MnPD. Furthermore, MnPD may serve as a mechanistic tool and indicate the new directions in the synthesis of catalase-like mimics.
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