Structure-activity studies on the protection of Trimetazidine derivatives modified with nitroxides and their precursors from myocardial ischemia-reperfusion injury

Tamás Kálai, Mahmood Khan, Mária Balog, Vijay Kumar Kutala, Periannan Kuppusamy, Kálmán Hideg

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5510-5516
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number16
DOIs
Publication statusPublished - Aug 15 2006

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Keywords

  • Langendorff-perfused heart
  • Nitroxides
  • ROS scavenging activity
  • Trimetazidine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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