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Author | dc.contributor.author | Galvis Pareja, David | |
Author | dc.contributor.author | Zapata Torres, Gerald | es_CL |
Author | dc.contributor.author | Hidalgo Tapia, Jorge | es_CL |
Author | dc.contributor.author | Ayala, Pedro | es_CL |
Author | dc.contributor.author | Pedrozo Cibils, Zully | es_CL |
Author | dc.contributor.author | Ibarra, Cristián | es_CL |
Author | dc.contributor.author | Díaz Araya, Guillermo | es_CL |
Author | dc.contributor.author | Hall, Andrew R. | es_CL |
Author | dc.contributor.author | Vicencio, José Miguel | es_CL |
Author | dc.contributor.author | Núñez Vergara, Luis | es_CL |
Author | dc.contributor.author | Lavandero González, Sergio | es_CL |
Admission date | dc.date.accessioned | 2014-12-11T15:40:34Z | |
Available date | dc.date.available | 2014-12-11T15:40:34Z | |
Publication date | dc.date.issued | 2014 | |
Cita de ítem | dc.identifier.citation | Toxicology and Applied Pharmacology 279 (2014) 53–62 | en_US |
Identifier | dc.identifier.other | DOI: 10.1016/j.taap.2014.05.004 | |
Identifier | dc.identifier.uri | https://repositorio.uchile.cl/handle/2250/121874 | |
General note | dc.description | Artículo de publicación ISI | en_US |
Abstract | dc.description.abstract | Rationale: Dihydropyridines are widely used for the treatment of several cardiac diseases due to their blocking
activity on L-type Ca2+ channels and their renowned antioxidant properties.
Methods: We synthesized six novel dihydropyridine molecules and performed docking studies on the binding
site of the L-type Ca2+ channel.We used biochemical techniques on isolated adult rat cardiomyocytes to assess
the efficacy of these molecules on their Ca2+ channel-blocking activity and antioxidant properties. The Ca2+
channel-blocking activity was evaluated by confocal microscopy on fluo-3AM loaded cardiomyocytes, as well
as using patch clamp experiments. Antioxidant properties were evaluated by flow cytometry using the ROS
sensitive dye 1,2,3 DHR.
Results: Our docking studies show that a novel compound with 3-OH substitution inserts into the active binding
site of the L-type Ca2+ channel previously described for nitrendipine. In biochemical assays, the novel meta-OH
group in the aryl in C4 showed a high blocking effect on L-type Ca2+ channel as opposed to para-substituted
compounds. In the tests we performed, none of the molecules showed antioxidant properties.
Conclusions: Only substitutions in C2, C3 and C5 of the aryl ring render dihydropyridine compounds with the
capacity of blocking LTCC. Based on our docking studies, we postulate that the antioxidant activity requires a
larger group than the meta-OH substitution in C2, C3 or C5 of the dihydropyridine ring.
© 2014 Elsevier | en_US |
Patrocinador | dc.description.sponsorship | This work was supported by
grant FONDAP 15130011 (SL), Anillo ACT 1111 (SL) and FONDECYT
1050761 (LNV). | en_US |
Lenguage | dc.language.iso | en | en_US |
Publisher | dc.publisher | Elsevier | en_US |
Type of license | dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Chile | * |
Link to License | dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/cl/ | * |
Keywords | dc.subject | Calcium | en_US |
Título | dc.title | A novel dihydropyridine with 3-aryl meta-hydroxyl substitution blocks L-type calcium channels in rat cardiomyocytes | en_US |
Document type | dc.type | Artículo de revista | |
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