卤化聚酮类抗生素zunyimycins抑菌及抗肿瘤活性初步分析
发布时间：2018-11-09 12:53
【摘要】：目的:对新型卤化二型聚酮类抗生素zunyimycins抑菌和抗肿瘤活性进行初步分析,为解析其活性机制提供实验依据。方法:(1)通过改变培养基组成、培养时间、培养方式等培养条件,优化zunyimycins高产量的培养条件;(2)利用“纸片扩散法”测定zunyimycins抑菌能力,“肉汤稀释法”检测最低抑菌浓度;(3)利用“MTT”法检测zunyimycin C对不同来源肿瘤细胞株的增殖抑制效应;并通过此方法检测zunyimycin C与硫辛酸联合用药对Hep G2肝癌细胞增殖的影响。结果:(1)在GYM固体培养基的基础上,添加1%腐殖酸乙醇浸出物,培养时间为17 d,目标化合物的产量提高;(2)zunyimycin A对临床分离菌株MRSA、粪肠球菌、枯草芽孢杆菌等测试菌的最小抑菌浓度分别为6.89μg/m L、16.71μg/m L和3.44μg/m L;zunyimycin B对临床分离菌株MRSA、粪肠球菌、枯草芽孢杆菌等测试菌的最小抑菌浓度分别为7.88μg/m L、12.81μg/m L和3.94μg/m L;zunyimycin C对临床分离菌株MRSA、粪肠球菌临床分离菌株、枯草芽孢杆菌等测试菌的最小抑菌浓度分别为3.75μg/m L、4.07μg/m L和0.938μg/m L;(3)zunyimycin C对Hep G2、Hep1、MKC45、SGC7901、A549、SCAP等细胞株的24 h半数抑制浓度分别为13.97μM、22.55μM、21.49μM、44.71μM、27.47μM和18.3μM;(4)8μM的zunyimycin C与硫辛酸联合用药时,可促进Hep G2细胞增殖;16μM和32μM的zunyimycin C与硫辛酸联合用药表现出对Hep G2细胞增殖抑制效应。结论:(1)在GYM培养基中添加1%的腐殖酸(乙醇浸出物),培养17 d后乙酸乙酯萃取,可提高zunyimycins类抗生素的产量;(2)zunyimycins对MRSA、肠球菌、枯草芽孢杆菌等革兰氏阳性菌表现出较好的抑制活性,其中zunyimycin C对临床分离MRSA和肠球菌等表现出较强的杀菌作用,可望用于治疗MRSA、VRE等致病菌的感染;(3)zunyimycin C可抑制Hep G2、A549及MKC45等癌细胞株的增殖,对抗肿瘤新药的开发具有重要的意义。
[Abstract]:Aim: to analyze the bacteriostatic and antitumor activities of zunyimycins, a new type of halogenated polyketone antibiotic, and to provide experimental evidence for elucidating the mechanism of its activity. Methods: (1) the culture conditions of high yield of zunyimycins were optimized by changing the culture conditions, such as composition of culture medium, culture time and culture method. (2) the bacteriostatic ability of zunyimycins was measured by "disk diffusion method", the minimum inhibitory concentration was detected by "broth dilution" method, (3) the inhibitory effect of zunyimycin C on the proliferation of tumor cell lines from different sources was detected by "MTT" method. The effect of zunyimycin C combined with lipoic acid on the proliferation of Hep G2 hepatoma cells was detected by this method. Results: (1) on the basis of GYM solid medium, adding 1% humic acid ethanol extract for 17 days, the yield of the target compound increased; (2) the minimal inhibitory concentrations of) zunyimycin A against the clinical isolates MRSA, Bacillus subtilis and Bacillus subtilis were 6.89 渭 g / mL and 3.44 渭 g / mL, respectively. The minimal inhibitory concentrations of zunyimycin B against Enterococcus faecalis and Bacillus subtilis were 7.88 渭 g / mL 12.81 渭 g / mL and 3.94 渭 g / mL, respectively. The minimal inhibitory concentrations of zunyimycin C against clinical isolates of Enterococcus faecalis and Bacillus subtilis were 3.75 渭 g / mL and 0.938 渭 g / mL, respectively. (3) the 24 h inhibitory concentrations of) zunyimycin C on Hep G2MKC45-HgC7901A549SCAP were 13.97 渭 M, 22.55 渭 M, 21.49 渭 M, 44.71 渭 M, 27.47 渭 M and 18.3 渭 M, respectively. (4) 8 渭 M zunyimycin C combined with lipoic acid could promote the proliferation of Hep G2 cells, and 16 渭 M and 32 渭 M zunyimycin C combined with lipoic acid could inhibit the proliferation of Hep G2 cells. Conclusion: (1) adding 1% humic acid (ethanol extract) into GYM medium and culture for 17 days can increase the yield of zunyimycins antibiotics. (2) zunyimycins showed good inhibitory activity against MRSA, Enterococcus, Bacillus subtilis and Gram-positive bacteria, among which zunyimycin C showed strong bactericidal effect on clinical isolation of MRSA and Enterococcus, which is expected to be used in the treatment of MRSA,. Infection of VRE and other pathogenic bacteria; (3) zunyimycin C can inhibit the proliferation of Hep G2A549 and MKC45, and has important significance in the development of new anti-tumor drugs.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R96
本文编号：2320471
[Abstract]:Aim: to analyze the bacteriostatic and antitumor activities of zunyimycins, a new type of halogenated polyketone antibiotic, and to provide experimental evidence for elucidating the mechanism of its activity. Methods: (1) the culture conditions of high yield of zunyimycins were optimized by changing the culture conditions, such as composition of culture medium, culture time and culture method. (2) the bacteriostatic ability of zunyimycins was measured by "disk diffusion method", the minimum inhibitory concentration was detected by "broth dilution" method, (3) the inhibitory effect of zunyimycin C on the proliferation of tumor cell lines from different sources was detected by "MTT" method. The effect of zunyimycin C combined with lipoic acid on the proliferation of Hep G2 hepatoma cells was detected by this method. Results: (1) on the basis of GYM solid medium, adding 1% humic acid ethanol extract for 17 days, the yield of the target compound increased; (2) the minimal inhibitory concentrations of) zunyimycin A against the clinical isolates MRSA, Bacillus subtilis and Bacillus subtilis were 6.89 渭 g / mL and 3.44 渭 g / mL, respectively. The minimal inhibitory concentrations of zunyimycin B against Enterococcus faecalis and Bacillus subtilis were 7.88 渭 g / mL 12.81 渭 g / mL and 3.94 渭 g / mL, respectively. The minimal inhibitory concentrations of zunyimycin C against clinical isolates of Enterococcus faecalis and Bacillus subtilis were 3.75 渭 g / mL and 0.938 渭 g / mL, respectively. (3) the 24 h inhibitory concentrations of) zunyimycin C on Hep G2MKC45-HgC7901A549SCAP were 13.97 渭 M, 22.55 渭 M, 21.49 渭 M, 44.71 渭 M, 27.47 渭 M and 18.3 渭 M, respectively. (4) 8 渭 M zunyimycin C combined with lipoic acid could promote the proliferation of Hep G2 cells, and 16 渭 M and 32 渭 M zunyimycin C combined with lipoic acid could inhibit the proliferation of Hep G2 cells. Conclusion: (1) adding 1% humic acid (ethanol extract) into GYM medium and culture for 17 days can increase the yield of zunyimycins antibiotics. (2) zunyimycins showed good inhibitory activity against MRSA, Enterococcus, Bacillus subtilis and Gram-positive bacteria, among which zunyimycin C showed strong bactericidal effect on clinical isolation of MRSA and Enterococcus, which is expected to be used in the treatment of MRSA,. Infection of VRE and other pathogenic bacteria; (3) zunyimycin C can inhibit the proliferation of Hep G2A549 and MKC45, and has important significance in the development of new anti-tumor drugs.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R96
【相似文献】
相关期刊论文 前2条
1 倪榴英;;多聚酮类抗生素生物合成的调节[J];国外医药(抗生素分册);1989年06期
2 叶卉;顾觉奋;;多环聚酮类抗生素abyssomicin C的研究进展[J];中国新药杂志;2011年23期
相关会议论文 前1条
1 贺强;孙锐;李爱英;;美达霉素的吡喃环形成相关基因的研究[A];2013年湖北省暨武汉微生物学会会员代表大会暨学术年会论文摘要集[C];2013年
相关硕士学位论文 前1条
1 王荫荫;卤化聚酮类抗生素zunyimycins抑菌及抗肿瘤活性初步分析[D];遵义医学院;2017年
，本文编号：2320471
本文链接：https://www.wllwen.com/yixuelunwen/yiyaoxuelunwen/2320471.html
最近更新
教材专著
