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1.
J Org Chem ; 83(17): 10501-10504, 2018 Sep 07.
Article in English | MEDLINE | ID: mdl-30101591

ABSTRACT

Unusual 1 JCH values for an oxocane derivative were recently reported, highlighting the unexpected long-range Perlin effect for the 1 JCH. According to our theoretical and experimental results listed in this paper, the previous published data cannot be supported. Moreover, when comparing the previously studied oxocane derivative with analogous molecules, we realized that the difference between J-couplings actually comes from the increase in the 1 JC-Hax instead of decreasing of 1 JC-Heq, as suggested.

2.
Bioorg Med Chem ; 23(15): 4397-4404, 2015 Aug 01.
Article in English | MEDLINE | ID: mdl-26122772

ABSTRACT

Cardiotonic steroids (CS), natural compounds with traditional use in cardiology, have been recently suggested to exert potent anticancer effects. However, the repertoire of molecules with Na,K-ATPase activity and anticancer properties is limited. This paper describes the synthesis of 6 new digoxin derivatives substituted (on the C17-butenolide) with γ-benzylidene group and their cytotoxic effect on human fibroblast (WI-26 VA4) and cancer (HeLa and RKO) cell lines as well as their effect on Na,K-ATPase activity and expression. As digoxin, compound BD-4 was almost 100-fold more potent than the other derivatives for cytotoxicity with the three types of cells used and was also the only one able to fully inhibit the Na,K-ATPase of HeLa cells after 24h treatment. No change in the Na,K-ATPase α1 isoform protein expression was detected. On the other hand it was 30-40 fold less potent for direct Na,K-ATPase inhibition, when compared to the most potent derivatives, BD-1 and BD-3, and digoxin. The data presented here demonstrated that the anticancer effect of digoxin derivatives substituted with γ-benzylidene were not related with their inhibition of Na,K-ATPase activity or alteration of its expression, suggesting that this classical molecular mechanism of CS is not involved in the cytotoxic effect of our derivatives.


Subject(s)
Antineoplastic Agents/chemical synthesis , Benzylidene Compounds/chemistry , Digoxin/analogs & derivatives , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Binding Sites , Brain/enzymology , Cell Line , Cell Survival/drug effects , Digoxin/chemical synthesis , Digoxin/toxicity , HeLa Cells , Humans , Kidney/enzymology , Molecular Docking Simulation , Protein Structure, Tertiary , Rats , Sodium-Potassium-Exchanging ATPase/metabolism
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