DEEPOXIDATION OF 16-MEMBERED EPOXYENONE MACROLIDE ANTIBIOTICS

III. IN VITRO AND IN VIVO EVALUATION OF DEEPOXIDATION PRODUCTS OF CARBOMYCIN A, DELTAMYCIN A₁, 4″-PHENYLACETYLDELTAMYCIN, ANGOLAMYCIN AND ROSAMICIN

Abstract

Deepoxidation products P1, P2 and P3 of carbomycin A, deltamycin A₁ and 4″-phenylacetyldeltamycin showed high in vitro antibacterial and antimycoplasmal activities which were comparable to those of the respective parent compounds. By contrast, the in vitro antimicrobial potencies of angolamycin P1 and rosamicin P1 were about ten-fold lower than those of the parent macrolides. In mice, the increase in the plasma levels of the epoxyenone macrolides due to deepoxidation was highly significant with the P1, P2 and P3 derivatives of carbomycin A and 4″-phenylacetyldeltamycin, whereas angolamycin P1 gave a moderately-improved plasma level compared with angolamycin.