Synthesis and studies of calcium channel blocking and antioxidant activities of...

• Autor(es): Rucins, Martins ; 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
• Data: 2014
• Identificador Persistente: http://hdl.handle.net/10316/25285
• Origem: Estudo Geral - Universidade de Coimbra
• Assunto(s): 1,4-Dihydropyridines; N-Dodecyl pyridinium; Propargyl substituent; Calcium antagonists; Antioxidant activity; Mitochondrial processes; Structure–activity relationships
• Tipo de Documento: Artigo
• Idioma: Inglês

Descrição

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. This study was supported by ESF project No. 2009/ 0217/1DP/1.1.1.2.0/09/APIA/VIAA/031; the EuroNanoMed project ‘‘CheTherDel’’; Portuguese Research Council (FCT), Faculty of Medicine, Centre for Neuroscience and Cell Biology (CNC) and Marine and Environmental Research Centre (IMAR–CMA) of the University of Coimbra, Portugal.