Synthesis and characterization of novel indole derivatives reveal improved therapeutic agents for treatment of ischemia/reperfusion (I/R) injury.
To develop more potent therapeutic agents with therapeutic efficacy for ischemia/reperfusion (I/R) injury, we linked an antiinflammatory moiety (1,3-dioxane derivative) to the key pharmacophoric moiety of melatonin. We hypothesized that the resulting new indole derivatives might induce a synergistic protection against oxidative damage associated with I/R injury. Our results indicate that one of these indole derivatives (7) manifests potent antiinflammatory antioxidant effects and exerts a protective effect against skeletal muscle injury and associated lung injury following limb I/R in rats.
Bi
Wei
W
Department of Chemistry, Michigan Technological University, Houghton, Michigan 49931, USA. biwei8115@sohu.com
Bi
Yue
Y
Xue
Ping
P
Zhang
Yanrong
Y
Gao
Xiang
X
Wang
Zhibo
Z
Li
Meng
M
Baudy-Floc'h
Michèle
M
Ngerebara
Nathaniel
N
Gibson
K Michael
KM
Bi
Lanrong
L
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002199:Capillary Permeability; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy; D015227:Lipid Peroxidation / Q000187:drug effects; D055370:Lung Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D016716:PC12 Cells; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016166:Free Radical Scavengers; D007211:Indoles