Drug design of medicinal products on the basis of natural cardiosteroids
The aim. The article describes works about designing a structure, predicting of biological activity and the chemical transformation of natural cardiosteroids to obtain promising drugs with specified properties.
Materials and methods. An effective modified method for the synthesis of aldimines of cardenolides, based on the interaction of natural cardenolides with organic amines, is proposed. The abnormal physical and chemical properties of bis-ketoimines, which consist in their resistance to hydrolysis and increased polarity, are revealed.
Results. It is revealed that electrostatic fields play a decisive role in cardiotonic activity, which should be located in the form of a “sandwich” – in the α-plane there is a positive charge and in the β-plane is negative. The presence of a negative field at C3 is mandatory and the activity is higher if this negative field is extended further (the sugar component of the conditioned configuration, which does not violate the charges of the α- and β-planes). It is shown why the molar activity (biological activity expressed in moles of substance per kg of animal mass) of cardenolide glycosides is higher than their aglycones, that is, the sugar component contributes to the activity through electron fields, and not only due to changes in the hydrophilic-lipophilic properties of the substance.
Conclusions. The hypothesis of the existence of a phenomenon of non-inducing binding to Na +, K + -AT Phase, in which the substance acts as an antidote for active cardiosteroids is formulated.
A detailed analysis of this relatively exceptional case involves the simultaneous occurrence of two isomerism – conformational (conformers) and geometric in the synthesis of aldimines of cardenolides\
How to cite paper:
Gubin, I., Romelashvili, O., & Zborovska, T. (2020). Drug design of medicinal products on the basis of natural cardiosteroids. ScienceRise: Pharmaceutical Science, (2 (24), 26–32. https://doi.org/10.15587/2519-4852.2020.201107