Synthesis and biological activity of hydrophosphoryl derivatives of nystatin

Synthesis and antifungal activity of N-trialkylsilyl derivatives of nystatin

“…The antifungal activity of nystatin derivatives I -V decreased with increases in the branching of the alkyl substituent at the silicon atom (Table 2). This appears to be due to steric factors hindering the formation of the complex between silicon-containing nystatin derivatives I -V and sterols (mainly ergosterol) in the cell membranes of fungal microorganisms, which is consistent with our previous results [36] and published data from recent years [48 -50].…”

“…The literature contains descriptions of a whole series of nystatin derivatives: esters [9 -12], N-acyl derivatives [13 -15], N-glycoside derivatives [16 -18], amides [19], hydrazides [10], and enamine and amidine [21], hydrophosphoryl [22], and organofluorine [23] derivatives, along with water-soluble salts and complexes [24 -28]. Special attention has in recent years been paid to liposomal derivatives of nystatin, which have significantly lower toxicity, better pharmacokinetic characteristics, and greater antibiotic stability [29 -32].…”

“…Silicon-containing derivatives of polyene macrolide antibiotics have not previously been described in the literature. We have published preliminary reports of the synthesis of the first silicon-containing derivatives of nystatin [36]. Continuing our studies on the synthesis of nystatin derivatives of this class, we investigated the silylation reaction and the antifungal activity of the resulting derivatives.…”

Organofluorine derivatives of nystatin

“…In recent years, the interest of researchers is drawn to the synthesis of functionally-substituted derivatives of this antibiotic [3 -5]. Previously we have reported on the synthesis of organosilicon [6] and hydrophosphoryl [7] derivatives of nystatin.In this communication we report on the reactions between nystatin and organofluorine compounds and the medico-biological properties of the resulting nystatin derivatives.It was established that interactions of nystatin with trifluoroacetic and perfluoropropionic anhydrides lead to the formation of the corresponding N-perfluoroacylnystatin derivatives (I and II).The structures of these organofiuorine derivatives were determined by methods of IH and 19F NMR spectroscopy and IR and UV spectrophotometry. The compositions are verified by elemental analyses whose data coincide with the results of analytical calculations based on the empirical formulas.…”