Evaluation of three 4"-deoxy-4"-sulfonamido-oleandomycin derivatives with erythromycin-like antibacterial potency

Abstract

Three derivatives of oleandomycin in which the C"-4 hydroxyl moiety was replaced for the first time with a nitrogen functionality have been compared with erythromycin base and oleandomycin base. The minimum inhibitory concentrations of these derivatives for 90% of a group of clinical isolates of Staphylococcus aureus were one-half to one-fourth those of erythromycin. The minimum inhibitory concentrations of the experimental macrolides for 50% of a group of S. aureus isolates resistant to greater than 12.5 micrograms of erythromycin per ml ranged from 0.2 to 0.39 micrograms/ml. The activities of these experimental compounds were equivalent to the activities of erythromycin against Staphylococcus epidermidis, Bacteroides fragilis, and Haemophilus influenzae isolates. In general, erythromycin was more active against Streptococcus species. Each experimental macrolide was superior to erythromycin in inhibiting RNA-directed, cell-free polypeptide synthesis. The three experimental compounds were markedly more active than erythromycin base after oral administration to mice infected with S. aureus. The 50% protective doses of the experimental compounds ranged from 27.4 to 45.7 mg/kg; that of erythromycin was approximately 100 mg/kg.

Synthesis and biological activities of 4"-deoxy-4"-sulfonamido-oleandomycin derivatives

“…Two heteroaromatic sulfonamides, C-17 and C-18, exhibited good oral in vivo efficacy. From this series of compounds, oleandomycin sulfonamides C-12, C-17, and C-18 were selected for further biological investigation, the results of which are reported in the accompanying communication (8).…”

Side chain modifications in lankacidin group antibiotics

“…However, as will be shown in the present work, both lankacidin and lankacidinol are at least equal to erythromycin as inhibitors of polypeptide synthesis in a cell-free system. Hence, the therapeutic potential of 17- (ii) Lankacidin diformate (2). A solution of 4.59 g (0.01 mol) of lankacidin and 50 ml of pyridine was cooled to 0 to 5°C.…”