ChemInform Abstract: A New Approach to the Design of Novel Inhibitors of Na+,K+-ATPase: 17α-Substituted Seco-D 5β-Androstane as Cassaine Analogues

Autor: Giorgio Fedrizzi, Paolo Barassi, Massimo Mabilia, Mauro Gobbini, Alberto Cerri, S. De Munari, Piero Melloni
Rok vydání: 2010
Předmět:
Zdroj: ChemInform. 29
ISSN: 1522-2667
0931-7597
DOI: 10.1002/chin.199849237
Popis: A new three-dimensional model for the relative binding mode of cassaine 1 and digitoxigenin 2 at the digitalis receptor site is proposed on the basis of the structural and conformational similarities among 1, 2 and its 14,15-seco analogues 3 and 4. Accordingly, the speculation that also 17alpha-substituted derivatives of the digitalis 5beta,14beta-androstane skeleton could efficiently bind to the Na+,K+-ATPase receptor is put forward and verified through the synthesis of some related compounds. The binding affinity shown by 2-(N,N-dimethylamino)ethyl 3beta, 14-dihydroxy-5beta,14beta-androstane-17alpha-acrylate 6 (IC50 = 5.89 microM) and, much more significantly, by the corresponding 14, 15-seco-14-oxo derivative 9 (IC50 = 0.12 microM) substantiates the new hypothesis and opens new prospects to the design of novel inhibitors of Na+,K+-ATPase as potential positive inotropic compounds.
Databáze: OpenAIRE
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