Norcia L J, Silvia A M, Dirlam J P, Schnur R C, Bergeron J M, Retsema J A, Hayashi S F
Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
J Antibiot (Tokyo). 1999 Nov;52(11):1007-16. doi: 10.7164/antibiotics.52.1007.
Two cyclic homopentapeptides, CP-101,680 and CP-163,234 [6a-(3',4'-dichlorophenylamino) analogs of viomycin and capreomycin, respectively], were identified as novel antibacterial agents for the treatment of animal disease, especially for livestock respiratory disease. The in vitro microbiological characterization of both CP-101,680 and CP-163,234 was carried out using their parent compounds, viomycin and capreomycin, as controls. This characterization included antibacterial spectrum, influence of media, inoculum size, pH, EDTA, polymixin B nonapeptide (PMBN), serum, cell-free protein synthesis inhibition, and time-kill kinetics. Our results indicated that the capreomycin analog, CP-163,234, showed slightly improved in vitro potency over the viomycin analog, CP-101,680. Both analogs showed very potent cell-free protein synthesis inhibition activity and were bactericidal against Pasteurella haemolytica, P. multocida and Actinobacillus pleuropneumoniae at the level of 4 times and 8 times MICs. CP-163,234 was bactericidal at the level of 4x and 8x MIC against E. coli, but re-growth was observed after 24 hours incubation at both concentrations of CP-101,680.
两种环状同型五肽，CP - 101,680和CP - 163,234（分别是紫霉素和卷曲霉素的6a -（3'，4'-二氯苯基氨基）类似物）被鉴定为治疗动物疾病，特别是家畜呼吸道疾病的新型抗菌剂。以它们的母体化合物紫霉素和卷曲霉素作为对照，对CP - 101,680和CP - 163,234进行了体外微生物学特性研究。该特性研究包括抗菌谱、培养基的影响、接种量、pH值、乙二胺四乙酸（EDTA）、多粘菌素B九肽（PMBN）、血清、无细胞蛋白质合成抑制以及时间 - 杀菌动力学。我们的结果表明，卷曲霉素类似物CP - 163,234在体外的效力比紫霉素类似物CP - 101,680略有提高。两种类似物均表现出非常强的无细胞蛋白质合成抑制活性，并且在4倍和8倍最小抑菌浓度（MIC）水平对溶血巴斯德菌、多杀性巴氏杆菌和胸膜肺炎放线杆菌具有杀菌作用。CP - 163,234在4倍和8倍MIC水平对大肠杆菌具有杀菌作用，但在CP - 101,680的两种浓度下孵育24小时后均观察到细菌再生长。
