Synthesis and biological evaluation of benzopyran analogues bearing class III antiarrhythmic pharmacophores

Maria Koufaki, Christina Kiziridi, Panagiota Papazafiri, Athanasios Vassilopoulos, Andràs Varró, Zsolt Nagy, Attila Farkas, Alexandros Makriyannis

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Abstract

We have synthesized a series of compounds combining the hydroxy-benzopyran ring of vitamin E with the methylsulfonylaminophenyl group of class III antiarrhythmic drugs, connected through tertiary amine moieties. Evaluation of the antiarrhythmic and antioxidant activity of the new compounds was carried out on isolated rat heart preparations using the non-recirculating Langendorff mode. The new analogues were present, at 10 μM concentration, during ischemia and reperfusion. Selected compounds were further studied by a conventional microelectrode method in order to get insight into their cellular mode of action. The most active compound, N-[4-[2-[[2-(3,4-dihydro-6-hydroxy-2,2,7,8-tetramethyl-2H-1-benzopyran-5 -yl)ethyl] methylamine]ethyl]phenyl]methanesulfonamide (19a), reduces premature beats, prolongs QT and QRS intervals during ischemia and reperfusion, and reduces MDA content, leading to a fast recovery of the heart. In addition, it exhibits moderate class III antiarrhythmic action.

Original languageEnglish
Pages (from-to)6666-6678
Number of pages13
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number19
DOIs
Publication statusPublished - Oct 1 2006

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Keywords

  • Antiarrhythmic agents
  • Benzopyran analogue
  • Cellular electrophysiology
  • Ischemia/reperfusion

ASJC Scopus subject areas

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

Cite this

Koufaki, M., Kiziridi, C., Papazafiri, P., Vassilopoulos, A., Varró, A., Nagy, Z., Farkas, A., & Makriyannis, A. (2006). Synthesis and biological evaluation of benzopyran analogues bearing class III antiarrhythmic pharmacophores. Bioorganic and Medicinal Chemistry, 14(19), 6666-6678. https://doi.org/10.1016/j.bmc.2006.05.065