【文章名】Chemical Modification and Biological Evaluation of New Semisynthetic Derivatives of 28,29-Didehydronystatin A1 (S44HP), a Genetically Engineered Antifungal Polyene Macrolide Antibiotic.
Chemical Modification and Biological Evaluation of New Semisynthetic Derivatives of 28,29-Didehydronystatin A1 (S44HP), a Genetically Engineered Antifungal Polyene Macrolide Antibiotic.
作者
Preobrazhenskaya, Maria N.;Olsufyeva, Evgenia N.;Solovieva, Svetlana E.;Tevyashova, Anna N.;Reznikova, Marina I.;Luzikov, Yuryi N.;Terekhova, Larisa P.;Trenin, Aleksei S.;Galatenko, Olga A.;Treshalin, Ivan D.;Mirchink, Elena P.;Bukhman, Vladimir M.;Sletta
[摘要]：Twenty-three new derivs. of the heptaene nystatin analog 28,29-didehydronystatin A1 (S44HP) were obtained by chem. modification of C16 carboxyl and amino groups of mycosamine. These derivs. comprised 15 carboxamides, 4 N-alkyl derivs., 3 N-derivs. contg. addnl. N-linked monosaccharide or disaccharide moiety (products of Amadori rearrangement), and 1 N-aminoacyl deriv. The derivs. have been tested in vitro against yeasts Candida albicans, Cryptococcus humicolus, and filamentous fungi (molds) Aspergillus niger and Fusarium oxysporum, as well as for hemolytic activity against human erythrocytes. Structure-activity relationships for the compds. obtained are discussed. The most active and least hemolytic deriv. 3-(N,N-dimethylamino)propylamide of S44HP was tested for acute toxicity and antifungal activity in animal model. Whereas amphotericin B and S44HP were active in vivo at doses close to the maximal tolerated dose, deriv. 3-(N,N-dimethylamino)propylamide of S44HP was considerably less toxic and more active compared to these two antibiotics.
