Synthesis and studies of calcium channel blocking and antioxidant activities of novel 4-pyridinium and/or N-propargyl substituted 1,4-dihydropyridine derivatives

Martins Rucins, Dainis Kaldre, Karlis Pajuste, Maria A.S. Fernandes, Joaquim A.F. Vicente, Linda Klimaviciusa, Elina Jaschenko, Iveta Kanepe-Lapsa, Irina Shestakova, Mara Plotniece, Marina Gosteva, Arkadij Sobolev, Baiba Jansone, Ruta Muceniece, Vija Klusa, Aiva Plotniece

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

The novel 1,4-dihydropyridine derivatives containing the cationic pyridine moiety at the position 4, and the N-propargyl group as a substituent at position 1 of the 1,4-DHP cycle were designed, synthesised, and assessed in biological tests. Among all the novel compounds, the 4-(N-dodecyl) pyridinium group-containing compounds 11 (without the N-propargyl group) and 12 (with the N-propargyl group) demonstrated the highest calcium antagonistic properties against neuroblastoma SH-SY5Y (IC50 about 5-14 μM) and the vascular smooth muscle A7r5 cell (IC50 - 0.6-0.7 μM) lines, indicating that they predominantly target the L-type calcium channels. These compounds showed a slight total antioxidant activity. At concentrations close to those of L-type calcium channel blocking ones, compound 12 did not affect mitochondrial functioning; also, no toxicity was obtained in vivo. The N-propargyl group as a substituent at position 1 of the 1,4-DHP cycle did not essentially influence the compounds' activity. The 4-(N-dodecyl) pyridinium moiety-containing compounds can be considered as prototype molecules for further chemical modifications and studies as cardioprotective/neuroprotective agents.

Original languageEnglish
Pages (from-to)69-80
Number of pages12
JournalComptes Rendus Chimie
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 2014
Externally publishedYes

Keywords*

  • 1,4-Dihydropyridines
  • Antioxidant activity
  • Calcium antagonists
  • Mitochondrial processes
  • N-Dodecyl pyridinium
  • Propargyl substituent
  • Structure-activity relationships

Field of Science*

  • 1.4 Chemical sciences
  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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