STRUCTURE ACTIVITY RELATIONSHIPS OF SYNTHETIC ANTIBIOTIC ANALOGUES OF CHRYSCANDIN

Anti-yeast activity with a series of chryscandin derivatives showed that theO-methyl-Ltyrosyl moiety is not always required for activity at the target site. On the other hand, the adenyl-3'-aminoribofuranuronic acid moiety seems to be essential for biological activity. Therefore, the various acyl derivatives on the amino group of the sugar part of the nucleoside were synthesized. 1-(6-Amino-9H-purin-9-yl)-3-(S-benzyl-L-cysteinylamino)-1, 3-dideoxy-β-D-ribofuranuronic acid (16) showed the highest efficacy among them againstCandida albicans. It exhibited sixteen-fold enhanced activityin vitro compared with that of native chryscandin. Thein vivo activity of16 against experimental infection ofC. albicans showed the almost same as that of 5-fluorocytosine and a superior to that of ketoconazole.