Cardiac glycosides : new trends in medicinal chemistry of saponins and their genins

Abstract

Plant secondary metabolites – ubiquitous low molecular weight chemicals which are not essentials for the host existence and reproduction but serve many auxiliary functions, are frequently occurring as glycosides, for which particularly abundant examples exist in antibiotic, saponins and flavonoid categories. Cardiac glycosides (CG), originally isolated from Digitalis plants, also known as cardiotonic steroids, have particularly extensive record of ethnopharmacological and medicinal use. Although their application in treatment of dropsy is documented since 1875, long time has elapsed before their chemical structure were determined and mechanisms of their toxicity and cardiotonic action were recognized as inhibition of Na+ / K+ ATP-ase pump. Contemporary molecular pharmacology has revealed that cardiac glycosides are endogenous compounds in variety of animals, where they function as toxins or hormones. Besides, numerous recent studies confirmed anticancer activity of CGs at very low concentrations. These findings have been possible due to advances in ultrasensitive analytical techniques and also due to progress in organic synthesis, particularly total enantioselective syntheses of carbohydrates, which secured availability of individual CG and their analogs for medicinal chemistry studies