title: Structure-activity studies on the protection of Trimetazidine derivatives modified with nitroxides and their precursors from myocardial ischemia-reperfusion injury.
abstract: Trimetazidine, the known anti-anginal and anti-ischemic drug, was modified by pyrroline and tetrahydropyridine nitroxides and their hydroxylamine and sterically hindered secondary amine precursors. The synthesized new compounds proved to be better superoxide scavenger molecules compared to the parent Trimetazidine in an in vitro experiment. This reactive oxygen species (ROS) scavenging activity was further supported by ischemia/reperfusion (I/R) studies on Langendorff-perfused rat hearts pretreated with Trimetazidine and with the modified Trimetazidine derivatives before ischemia. Two of the investigated compounds, containing 2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole and 4-phenyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole substituents on the piperazine ring, provided significant protection from the cardiac dysfunction caused by I/R. The protective effect could be attributed to the combined anti-ischemic and antioxidant effects.
authors.affiliation: Institute of Organic and Medicinal Chemistry, University of Pécs, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Kálai
authors.forename: Mahmood
authors.initials: M
authors.lastname: Khan
authors.forename: Mária
authors.initials: M
authors.lastname: Balog
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Kutala
authors.forename: Periannan
authors.initials: P
authors.lastname: Kuppusamy
authors.forename: Kálmán
authors.initials: K
authors.lastname: Hideg
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000473:pathology* / Q000517:prevention & control; D009589:Nitrogen Oxides / Q000737:chemistry*; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014292:Trimetazidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D009589:Nitrogen Oxides; D010879:Piperazines; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D000077489:Piperazine; D014292:Trimetazidine