Journal
COMPTES RENDUS CHIMIE
Volume 17, Issue 1, Pages 69-80Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.crci.2013.07.003
Keywords
1,4-Dihydropyridines; N-Dodecyl pyridinium; Propargyl substituent; Calcium antagonists; Antioxidant activity; Mitochondrial processes; Structure-activity relationships
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Funding
- ESF [2009/0217/1DP/1.1.1.2.0/09/APIA/VIAA/031]
- EuroNanoMed project CheTherDel
- Portuguese Research Council (FCT)
- Faculty of Medicine
- Centre for Neuroscience and Cell Biology (CNC)
- Marine and Environmental Research Centre (IMAR-CMA) of the University of Coimbra, Portugal
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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 mu M) and the vascular smooth muscle A7r5 cell (IC50 - 0.6-0.7 mu M) 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. (C) 2013 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
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