新克拉维烷抗生素G0069的研究

A STUDY OF NEW CLAVAM ANTIBIOTICS G0069

在筛选新抗生素的工作中,我们于1983年由西双版纳土样中筛出放线菌G0069。经初步分类研究认为应属链霉菌吸水类群。对该菌做了相应的发酵研究。经提取鉴别,证实该菌产生三个抗生素G0069A、B及C。其中A、C为新克拉维烷抗生素。对G0069A组份的生物活性做了一些研究。G0069A有较弱的抗酵母样菌活性,抗丝状真菌更弱,不抗细菌。但组织培养有抑制KB细胞的活性,其作用方式为time dependent型。G0069A抗瘤谱显示其抗瘤作用是有选择性的,该组分对人实体瘤抑制效果较强,对小鼠、大鼠和地鼠肿瘤抑制效果较差。

Three antibiotics, designated as G0069 A, B and C, were isolated from a strain of Streptomyces hygroscoptcus G0069, in 1983. The strain -was isolated from a soil sample collected in Xishuang banna, a subtropic region in Guangxi Zhuang Nationality Autonomous Region, China. The fermentation, isolation and purification of these antibiotics was reported. Based on the results of mass spectrum, 1H- and 13C-NMR spectra, IR, UV and amino acid analysis, antibiotics G0069 A, B and C were identified to be the clavam antibiotics. Antibiotics G0069 A and C, having a clavam skeleton each, with a serine·valine or a serine · alanine side chain respectively, were considered to be two new clavam antibiotics. The major component G0069 A was studied in detail. Antibiotic G0069 A has weak inhibitory effect against some yeasts and filamentous fungi, but has no antibacterial activity, even with some other βb-lactam antibictics in combination. Antibiotic G0069 A displayed negative results in the concentrations from 62,5μg/ml to l,000μg/ml tested in spermatogonial assay, and exhibited toxic effect at 1,000Mg/ml. But it showed strong growth inhibitory effect on KB cells.On the contrary, other β-lacturu antibiotics showed negative results. The action of antibiotic G0069 A on KB cells was assumed as the compound of the time-dependent type. Forteen culture cell lines were further used to test the growth inhibitory effects of G0069 A. It showed that antibiotic G0069 A has stronger efficacies (ED60 0.1μg/ml) against human neoplastic cell lines derived from solid cancer than the neoplastic cells originated from mouse or rat. But it showed no increase of the life span of BDF1 mice inoculated with p388 leukemia cells in any administration schedules. The negative results of in vivo test might be correlated to the combination of G006.9 A with rat serum protein.