Manganese-based complexes of radical scavengers as neuroprotective agents.
Manganese was incorporated in the structure of the selected antioxidants to mimic the superoxide dismutase (SOD) and to increase radical scavenging ability. Five manganese complexes (1-5) showed potent SOD activity in vitro with IC(50) of 1.18-1.84 microM and action against lipid peroxidation in vitro with IC(50) of 1.97-8.00 microM greater than their ligands and trolox. The manganese complexes were initially tested in vivo at 50 mg/kg for antagonistic activity on methamphetamine (MAP)-induced hypermotility resulting from dopamine release in the mice brain. Only manganese complexes of kojic acid (1) and 7-hydroxyflavone (3) exhibited the significant suppressions on MAP-induced hypermotility and did not significantly decrease the locomotor activity in normal condition. Manganese complex 3 also showed protective effects against learning and memory impairment in transient cerebral ischemic mice. These results supported the brain delivery and the role of manganese in SOD activity as well as in the modulation of brain neurotransmitters in the aberrant condition. Manganese complex 3 from 7-hydroxyflavone was the promising candidate for radical implicated neurodegenerative diseases.
Vajragupta
Opa
O
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Road, Bangkok 10400, Thailand. pyovj@mahidol.ac.th
Boonchoong
Preecha
P
Sumanont
Yaowared
Y
Watanabe
Hiroshi
H
Wongkrajang
Yuvadee
Y
Kammasud
Naparat
N
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy; D004298:Dopamine / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D007858:Learning / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008345:Manganese / Q000737:chemistry; D008569:Memory Disorders / Q000517:prevention & control; D008694:Methamphetamine; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D013619:Tacrine / Q000737:chemistry
D000975:Antioxidants; D005419:Flavonoids; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D009942:Organometallic Compounds; D008345:Manganese; D008694:Methamphetamine; D013619:Tacrine; D013482:Superoxide Dismutase; D004298:Dopamine; C429845:7-hydroxyflavone