Identification, biological activity, and mechanism of the anti-ischemic quinolone analog

• Published in: Bioorganic & medicinal chemistry 2007-10, Vol.15 (20), p.6517-6526
• Main Authors: Park, Chan-Hee, Lee, Jongwon, Jung, Hwi Young, Kim, Min Ji, Lim, Sun Ha, Yeo, Hyung Tae, Choi, Eung Chil, Yoon, Eun Jeong, Kim, Kyu Won, Cha, Jong Ho, Kim, Seok-Ho, Chang, Dong-Jo, Kwon, Do-Yeon, Li, Funan, Suh, Young-Ger
• Format: Article
• Language: English
• Subjects: Animals; Anti-apoptotic activity; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-ischemic agents; Biological and medical sciences; Brain Ischemia - drug therapy; Brain Ischemia - pathology; Cardiovascular system; Cell Line, Tumor; Cell Survival - drug effects; Disease Models, Animal; Humans; MCAO; Medical sciences; Miscellaneous; Models, Biological; Molecular Structure; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Neuropharmacology; Pharmacology. Drug treatments; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Quinolines - therapeutic use; Quinolone analog; Rats; Structure-Activity Relationship
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2007.07.009

The quinolone analog SQ-4004 has been identified as a potentially excellent anti-ischemic agent, which exhibited highly potent efficacy in reducing infarct volume size in in vivo rat MCAO model (32.1% at 0.01 mg/kg) and potent cardioprotective effect at myocardial infarction in vivo model (26.6% at 0.01 mg/kg) while it exhibited highly reduced anti-bacterial activity. The quinolone analog SQ-4004 has been identified as a potentially excellent anti-ischemic agent, which exhibited highly potent efficacy in reducing infarct volume size in vivo rat MCAO model (32.1% at 0.01 mg/kg) and potent cardioprotective effect at myocardial infarction in vivo model (26.6% at 0.01 mg/kg) while it exhibited highly reduced anti-bacterial activity. The mechanistic study revealed that the anti-ischemic activity might exert via an anti-apoptotic pathway, which implies its therapeutic uses against the ischemic cell injuries including ischemic stroke and ischemic heart disease.