Inotropic Activity of Hydroindene Amidinohydrazones
| Autor: | M. Medarde, E. Caballero, Arturo San Feliciano, F. Tome, C. P. Melero, Rosalía Carrón, Käthi Geering, Luis Garcia Sevillano, Gilles Crambert, L. G. Lelievre |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Chronotropic Inotrope Cardiotonic Agents Digoxin Stereochemistry Guinea Pigs Amidines Nitro compound In Vitro Techniques Pharmacology Transfection Isozyme Xenopus laevis Heart Rate Drug Discovery medicine Animals Humans Potency Enzyme Inhibitors chemistry.chemical_classification biology Chemistry Hydrazones Biological Transport Heart Myocardial Contraction Rats Isoenzymes Indenes Enzyme inhibitor Oocytes biology.protein Molecular Medicine Female Sodium-Potassium-Exchanging ATPase Enantiomer medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 45:127-136 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm0109309 |
| Popis: | Several hydroindenic derivatives (7a-methyl-2,3,5,6,7,7a-hexahydro-1H-indenes), bearing an amidinohydrazone at C-5 and different moieties at C-1, have been synthesized and evaluated for their inotropic and chronotropic effects on right- and left-guinea-pig-atria activity. Three of them showed the same profile as digoxin, although with lower potency. The effect on Na(+),K(+)-ATPase (NKA) was also evaluated for these three compounds, observing that two of them, with the same absolute configuration as natural cardenolides, are also NKA inhibitors, while the compound with the opposite configuration lacks such an effect. More interestingly, both active compounds act without affecting the cardiac rhythm. This could be related to the selective inhibition of the human alpha2beta1 isozyme (associated with the inotropic effect) with respect to the alpha1beta1 isozyme (associated with the maintenance of basal ionic levels in the cell and the toxic effect of cardenolides). |
| Databáze: | OpenAIRE |
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