Development of a novel brain protectant

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15143
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Kumamoto University
• Principal Investigator: Otsuka Masami 熊本大学, 大学院生命科学研究部(薬), 教授 (40126008)
• Co-Investigator(Renkei-kenkyūsha): FUJITA Mikako 熊本大学, 薬学部, 准教授 (00322256) ; OKAMOTO Yoshinari 熊本大学, 大学院生命科学研究部, 助教 (20194409)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 脳保護薬 / HNE

Outline of Final Research Achievements

Cerebral ischemia generates oxygen free radical that induces lipid peroxidation of cerebral cell membrane to produce HNE that is toxic to cerebral nerve cells. The present research aimed at the development of a brain protecting drug that inactivates HNE.It was known that Carnosine (CAR) quenches HNE to form cyclic adduct. Histidine Hydrazide (HH) is also known to produce the similar adduct.
We now designed a compound named CNN that could form bicyclic HNE adduct that seems more stable compared with CAR or HH. CNN was found to quench HNE much more efficiently compared with CAR or HH. CNN rescued the death of PC-12 cell induced by HNE. CNN is effective by ip administration. CNN rescued the hippocampal CA1 cell death of transient cerebral ischemia model of Mongolian gerbil whereas HH did not. We developed CNN that efficiently inactivates neurotoxic HNE, the end-product of the lipid peroxidation.

Free Research Field

生体機能分子合成学