0000000000380676
AUTHOR
Maria A.s. Fernandes
Comparative study of taurine and tauropyrone: GABA receptor binding, mitochondrial processes and behaviour.
Abstract Objectives Taurine, a sulfur-containing amino acid, has high hydrophilicity and is poorly absorbed. Tauropyrone, a taurine-containing 1,4-dihydropyridine derivative, is suggested to have greater activity than taurine owing to improved physicochemical properties that facilitate delivery of the compound to target cells. The aim of this study was to determine whether the 1,4-dihydropyridine moiety in tauropyrone improves the pharmacological efficacy of taurine in vitro and in vivo. Methods The effects of taurine and tauropyrone, as well as of the 1,4-dihydropyridine moiety were compared in in-vitro experiments to determine the binding to GABA receptors and influence on mitochondrial p…
Targeting the Mitochondria by Novel Adamantane-Containing 1,4-Dihydropyridine Compounds
Linda Klimaviciusa1, Maria A. S. Fernandes2, Nelda Lencberga1, Marta Pavasare1, Joaquim A. F. Vicente2, Antonio J. M. Moreno2, Maria S. Santos3, Catarina R. Oliveira4, Imanta Bruvere5, Egils Bisenieks5, Brigita Vigante5 and Vija Klusa1 1Department of Pharmacology, Faculty of Medicine, University of Latvia, Riga 2IMAR-CMA, Department of Life Sciences, University of Coimbra, Coimbra 3CNC, Department of Life Sciences, University of Coimbra, Coimbra 4CNC, Faculty of Medicine, University of Coimbra, Coimbra 5Laboratory of Membrane Active and beta-Diketone Compounds, Latvian Institute of Organic Synthesis, Riga 2,3,4Portugal 1,5Latvia
Synthesis and studies of calcium channel blocking and antioxidant activities of novel 4-pyridinium and/or N-propargyl substituted 1,4-dihydropyridine derivatives
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 act…
Mitochondria as the target for mildronate's protective effects in azidothymidine (AZT)-induced toxicity of isolated rat liver mitochondria
Previously mildronate, an aza-butyrobetaine derivative, was shown to be a cytoprotective drug, through its mechanism of action of inhibition of carnitine palmitoyltransferase-1, thus protecting mitochondria from long-chain fatty acid accumulation and subsequent damage. Recently in an azidothymidine (AZT)-induced cardiotoxicity model in vivo (in mice), we have found mildronate's ability of protecting heart tissue from nuclear factor kappaB abnormal expression. Preliminary data also demonstrate cerebro- and hepatoprotecting properties of mildronate in AZT-toxicity models. We suggest that mildronate may target its action predominantly to mitochondria. The present study in isolated rat liver mi…