Cardiac steroids (CSs) are natural products that are involved in a broad range of biological and medicinal activities including congestive heart failure treatment, anti-cancer, anti-inflammatory, anti-malarial and anti-viral activities. The most commonly used CS for the treatment of heart failure and of chronic atrial fibrillation is the digoxin. It has been established CSs exert their cardiac activity by blocking Na+/K+ channels of heart muscle cells yet, the exact structure activity relationship (SAR) of their carbohydrate segments have not yet been established.
In an attempt to understand the biological role of CS carbohydrates and more specifically their effect on arrhythmic movements of myocardial cells, we designed and synthesized combinatorial library of betulin glycosides based CSs and studied their SAR on the contraction rate and cell shape of rat heart muscle cells. Similar to the clinically use digoxin, the synthesized betulin glycosides were found to affect the cell movement and contraction pace of fetal rat myocardial cells. The synthesis of two novel families of mono-glycosylated betulin derivatives and of a sub-family of di-glycosylated betulin derivatives and the effect of these novel CSs on cardiac activity of these compounds are discussed.
