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

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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

Fingerprint

Bearings (structural)
Benzopyrans
Reperfusion
Ischemia
Premature Cardiac Complexes
Microelectrodes
Anti-Arrhythmia Agents
Vitamin E
Amines
Rats
Antioxidants
Recovery

Keywords

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

ASJC Scopus subject areas

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

Cite this

Synthesis and biological evaluation of benzopyran analogues bearing class III antiarrhythmic pharmacophores. / Koufaki, Maria; Kiziridi, Christina; Papazafiri, Panagiota; Vassilopoulos, Athanasios; Varró, A.; Nagy, Zsolt; Farkas, Attila; Makriyannis, Alexandros.

In: Bioorganic and Medicinal Chemistry, Vol. 14, No. 19, 01.10.2006, p. 6666-6678.

Research output: Contribution to journalArticle

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, vol. 14, no. 19, pp. 6666-6678. https://doi.org/10.1016/j.bmc.2006.05.065
Koufaki, Maria ; Kiziridi, Christina ; Papazafiri, Panagiota ; Vassilopoulos, Athanasios ; Varró, A. ; Nagy, Zsolt ; Farkas, Attila ; Makriyannis, Alexandros. / Synthesis and biological evaluation of benzopyran analogues bearing class III antiarrhythmic pharmacophores. In: Bioorganic and Medicinal Chemistry. 2006 ; Vol. 14, No. 19. pp. 6666-6678.
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