Abstract
Inhibitors for polyamine oxidizing enzymes, spermine oxidase (SMOX) and N1-acetylpolyamine oxidase (PAOX), were designed and evaluated for their effectiveness in a photochemically induced thrombosis (PIT) mouse model. N1-Nonyl-1,4-diaminobutane (C9-4) and N1-tridecyl-1,4-diaminobutane (C13-4) competitively inhibited the activity of PAOX and SMOX in a manner comparable to N1,N4-bis(2,3-butadienyl)-1,4-butanediamine (MDL72527), an irreversible inhibitor of both enzymes. The two compounds were then tested for their effects in the PIT model. Both intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of C9-4 decreased infarct volumes significantly. By contrast, C13-4 reduced the volume of brain infarction by i.c.v. administration, but no reduction was observed after i.p. administration. C9-4 administered by i.p. injection reduced the volume of brain infarction significantly at doses of more than 3 mg/kg, and the dosage of 5 mg/kg or 10 mg/kg demonstrated the most potent effect and were more effective than equivalent doses of the other inhibitors such as MDL72527 and N-benzylhydroxylamine. I.P. injection of 5 mg/kg of C9-4 provided a therapeutic time window of longer than 12 h. This report demonstrates that C9-4 ...Continue Reading
References
Aug 18, 1992·Biochemical Pharmacology·P R Libby, C W Porter
Jan 1, 1985·Journal of Medicinal Chemistry·P BeyP Casara
May 3, 2003·Biochemical and Biophysical Research Communications·Yanlin WangRobert A Casero
Mar 26, 2005·Cancer Chemotherapy and Pharmacology·Yanlin WangRobert A Casero
Feb 14, 2006·Brain Research·Jun LiKaren M Doyle
Feb 21, 2006·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Hassan Pajouhesh, George R Lenz
Nov 23, 2006·Brain : a Journal of Neurology·Giuseppe PignataroZhi-Gang Xiong
May 13, 2008·Lancet·Geoffrey A DonnanStephen M Davis
Aug 21, 2008·Amino Acids·Koichi TakaoAkira Shirahata
Jul 16, 2009·IUBMB Life·Anthony E Pegg
Dec 29, 2010·Biochemical and Biophysical Research Communications·Ryotaro SaikiKazuei Igarashi
Jun 21, 2011·Experimental Physiology·Adam P MeccaColin Sumners
Feb 4, 2012·Journal of Enzyme Inhibition and Medicinal Chemistry·Manuela CervelliPaolo Mariottini
Sep 18, 2012·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Juan CenBian-Sheng Ji
Mar 2, 2013·Biological & Pharmaceutical Bulletin·Koichi TakaoYoshiaki Sugita
May 15, 2013·Free Radical Biology & Medicine·Caterina CaponeTiziana Persichini
Jun 4, 2013·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·Kazuo MinematsuUNKNOWN Japan Stroke Society
Nov 15, 2013·Chemical Research in Toxicology·Anthony E Pegg
Mar 4, 2014·Biological & Pharmaceutical Bulletin·Shun-suke MoriyaMasao Kawakita
Feb 20, 2016·PloS One·Roberta MastrantonioTiziana Persichini
Apr 3, 2016·Biochemical and Biophysical Research Communications·Takeshi UemuraKazuei Igarashi
Jun 19, 2016·Experimental Neurology·Takeru ShimizuPaco S Herson
Jun 6, 2017·Circulation Journal : Official Journal of the Japanese Circulation Society·Naoyuki TakashimaKazuhiko Nozaki
Dec 14, 2017·International Journal of Molecular Sciences·Mohamad El Amki, Susanne Wegener
Citations
Oct 20, 2018·The Journal of Biological Chemistry·Tracy Murray StewartRobert A Casero
Sep 6, 2018·Nature Reviews. Cancer·Robert A CaseroAnthony E Pegg
Jun 14, 2019·MedChemComm·Steven HolshouserPatrick M Woster