[Studies on acetylspiramycin. II. Biological activities of spiramycin components].
Acetylspiramycin (ASPM) was fractionated using high performance liquid chromatography (HPLC). The peak fractions were named F1 to F7 successively in order of increasing retention times (Rt), i.e., increasing hydrophobicity, and studied for 1) antibacterial activities (MIC), 2) antibacterial potency against Bacillus subtilis ATCC 6633, 3) therapeutic effect on mice infected with Streptococcus pneumoniae III, Staphylococcus aureus Smith, 4) acute toxicity by i.p. administration to mice (LD50) and 5) cytotoxicities to fibroblasts derived from Chinese-hamster lung (CHL), cow pulmonary artery endothelial cells (CPAE) and rat hepatic cells. The results obtained are summarized below. 1. Components F1 and 4'-acetylspiramycin F2 had significantly different biological activities from those of other components: F1 showed the lowest antibacterial potency of 492 micrograms (potency)/mg, F2 showed the highest antibacterial potency of 2,040 micrograms (potency)/mg and correspondingly the lowest LD50 value of 692 mg/kg (the highest toxicity). The therapeutic effect of F2 on infections in mice was found to be the second smallest and was superior only to that of F1. The LD50 value of F1 was 1,200 mg/kg and similar to that of ASPM. 2. Antibacterial potencies of F3, F4, F5 and F6 were 1,165, 1,266, 1,374 and 1,530 micrograms (potency)/mg, respectively; fraction with the higher antibacterial activities corresponded to the longer retention times, i.e., the greater hydrophobicities. The most hydrophobic component, F7, 3-propionyl-3",4"-diacetylspiramycin, however, showed a low antibacterial potency of 1,085 micrograms (potency)/mg, next to the lowest one, F1, a fact which was in contradiction to with the sequential relation between hydrophobicities and potencies from F3 to F6.(ABSTRACT TRUNCATED AT 250 WORDS)
Kondo
A
A
Quality Assurance & Services Department, Kyowa Hakko Kogyo Co., Ltd.
Sato
K
K
Shuto
K
K
Yamashita
K
K
Ichikawa
S
S
Takahashi
K
K
Kita
K
K
Nishiie
Y
Y
Sano
H
H
Yamaguchi
K
K
D000818:Animals; D001412:Bacillus subtilis / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D007928:Lethal Dose 50; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D011008:Pneumococcal Infections / Q000188:drug therapy; D051381:Rats; D015572:Spiramycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D013203:Staphylococcal Infections / Q000188:drug therapy
C033163:acetylspiramycin; D015572:Spiramycin