Synthetic chemotherapeutic drugs for the treatment of mycoses (review)

Chemical modification of heptaene macrolide antibiotic Amphotericin B under conditions of the Atherton-Todd reaction

“…Growing prospects of Amphotericin B application are due to the possibility of its use in complex with synthetic antifungal drugs in mycotic infections treatment [14][15][16]; furthermore, to revealing the antiviral [17,18] and antitumor [19,20] activity on this antibiotic. On top of it, Amphotericin B is promising for treatment of leishmaniasis [21][22][23], as antiinflammatoty drug [24], in genetic therapy [25], and for therapy of severe fungal sepsis (in combination with antibodies) [26,27] as well as of AIDS-complicating fungal diseases [28][29][30].…”

“…On top of it, Amphotericin B is promising for treatment of leishmaniasis [21][22][23], as antiinflammatoty drug [24], in genetic therapy [25], and for therapy of severe fungal sepsis (in combination with antibodies) [26,27] as well as of AIDS-complicating fungal diseases [28][29][30]. However, Amphotericin B is known for high toxicity (mainly nephrotoxicity) [9,11,31], low gastroenteric absorptivity [32,33], a number of side effects [3,14], and a reduced resistance of certain pathogenic fungi to Amphotericin B action [34,35]; therefore studies of various derivatives of this antibiotics have been emerging [36][37][38][39]. In earlier studies we prepared hydrophosphoryl [40], fluoroorganic [41], and N-benzyl derivatives of Amphotericin B [42].…”

Synthesis and antifungal activity of N-benzyl derivatives of amphotericin B

“…Nevertheless, the high toxicity (in particular, nephrotoxicity) of amphotericin B [24 -26], the low absorption from the gastrointestinal tract and poor penetration into cerebrospinal fluid [2,3,6], a whole series of side reactions [27], and the reduced sensitivity to it of pathogenic fungal microorganisms [28,29] have stimulated vigorous searches for different derivatives of this polyene antibiotic. The preparation of semisynthetic derivatives of amphotericin B with improved chemotherapeutic properties has been reviewed several times [5,23,30,31].…”