title: Discovery of 6-[4-(6-nitroxyhexanoyl)piperazin-1-yl)]-9H-purine, as pharmacological post-conditioning agent.
abstract: Novel purine analogues bearing nitrate esters were designed and synthesized in an effort to develop compounds triggering endogenous cardioprotective mechanisms such as ischemic preconditioning (IPC) or postconditioning (PostC). The majority of the compounds reduced infarct size compared to the control group in anesthetized rabbits, whereas administration of the most active analogue 16 at a dose of 3.8 μmol/kg resulted on a significant reduction of infarct size, compared to PostC group (13.4 ± 1.9% vs 26.4 ± 2.3%). These findings introduce a novel class of promising pharmacological compounds that could be used as mimics or enhancers of PostC.
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48, Vas. Constantinou Ave. 11635 Athens, Greece. mkoufa@eie.gr
authors.forename: Maria
authors.initials: M
authors.lastname: Koufaki
authors.forename: Theano
authors.initials: T
authors.lastname: Fotopoulou
authors.forename: Efstathios K
authors.initials: EK
authors.lastname: Iliodromitis
authors.forename: Sophia-Iris
authors.initials: SI
authors.lastname: Bibli
authors.forename: Anastasia
authors.initials: A
authors.lastname: Zoga
authors.forename: Dimitrios Th
authors.initials: DT
authors.lastname: Kremastinos
authors.forename: Ioanna
authors.initials: I
authors.lastname: Andreadou
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D057775:Ischemic Postconditioning / Q000379:methods*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009566:Nitrates / Q000737:chemistry / Q000627:therapeutic use; D011687:Purines / Q000737:chemistry* / Q000627:therapeutic use*; D011817:Rabbits
chemical_list: D002316:Cardiotonic Agents; D009566:Nitrates; D011687:Purines