Luisa Quadri

Involvement of the Na+,K+-ATPase and its inhibitors in cardiovascular diseases

+,K+-ATPase inhibitors have been shown to be effective in the treatment of congestive heart failure and cardiac arrhythmias. The Digitalis Investigation Group (DIG) trial has demonstrated that long-term digoxin treatment improves symptoms of congestive heart failure and the quality of life in patients and, unlike cyclic adenosine monophosphatase (cAMP) dependent positive inotropes, does not have a negative effect on survival. Recently, evidence has been provided that the Na+,K+-ATPase may also be functionally modulated by endogenous inhibitors, such as ouabain-like factor (OLF). Elevated OLF levels have been documented in pathological conditions, such as cardiovascular disorders and particular genetic or essential forms of human hypertension. Na+,K+-ATPase and OLF could represent a novel pharmacological target for the treatment of those forms of hypertension sustained by this mechanism. This review will cover patenting activity in this field of research and will focus on the more significant patents publi...

Synthesis and biological evaluation of 2-Hydroxy derivatives of digitoxigenin and 3-Epidigitoxigenin

The four stereoisomers of the 2-hydroxy derivatives of digitoxigenin and 3-epidigitoxigenin have been synthesized, their structures established by NMR, and their binding affinity for the digitalis receptor on Na+, K(+)-ATPase evaluated. These derivatives showed lower affinities than the parent compounds. The hydrophilic hydroxy groups in the alpha position are more detrimental to the affinity than hydroxy groups in the beta position.