THE DEVELOPMENT OF INTELLECTUAL COMPUTER SYSTEM FOR RATIONAL DESIGN AND PREPARATION OF NOVEL SEMISYNTHETIC DERIVATIVES OF POLYENE MACROLIDE ANTIBIOTICS

Polyene macrolide antibiotics (PMA) form a large group of natural compounds that exhibit activity against yeasts and yeast-like and mycelial fungi, both saprophytic and pathogenic species. The potential for medicinal application of PMA increased owing to the discovery of their antiviral activity, activity against parasitic protozoa, and the ability to use these antifungal antibiotics as potential antitumor preparations. PMA are especially important for treating fungal diseases that complicate AIDS. Furthermore, PMA that are used in medical practice do not completely meet the needs of physicians because of their limited effectiveness and unsuitability for treating several types of serious mycoses. Barriers to the use of these drugs in medical practice are also their high toxicity, poor solubility in water, and reduced sensitivity to them of pathogenic fungal microorganisms. Therefore, search for novel derivatives of polyene macrolide antibiotics, possessing improved medical and biological properties, is a very urgent target.

The various semisynthetic derivatives of PMA, obtained by chemical modification, have been prepared by us. Thus, we have synthesized organophosphorus, organofluorine, organosilicon, N-benzyl-, N-aryl-substituted and others functionally substituted derivatives of PMA with high antifungal activity and low toxicity.

The Intellectual Computer System (ICS) for correct choice of the conditions for rational design and synthesis of new derivatives of PMA, which are depending from taxonomic type and characteristics of pathogenic fungi, was developed. ICS structure includes all specific data of pathogenic fungi, chemical and physical properties of semisynthetic derivatives of PMA, recommendations for their synthesis and using for the treatment of various fungal infections. Thus, application of ICS allows to reduce general duration of the preparation of new derivatives of PMA and increase therapeutic efficiency of their application.