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

• Autor(a) principal: Rucins, Martins
• Data de Publicação: 2014
• Outros Autores: Kaldre, Dainis, Pajuste, Karlis, Fernandes, Maria A. S., Vicente, Joaquim A. F., Klimaviciusa, Linda, Jaschenko, Elina, Kanepe-Lapsa, Iveta, Shestakova, Irina, Plotniece, Mara, Gosteva, Marina, Sobolev, Arkadij, Jansone, Baiba, Muceniece, Ruta, Klusa, Vija, Plotniece, Aiva
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/25285; https://doi.org/10.1016/j.crci.2013.07.003
• topic: 1,4-Dihydropyridines; N-Dodecyl pyridinium; Propargyl substituent; Calcium antagonists; Antioxidant activity; Mitochondrial processes; Structure–activity relationships

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 mM) and the vascular smooth muscle A7r5 cell (IC50 – 0.6–0.7 mM) 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.