鹵化聚酮類抗生素zunyimycins抑菌及抗腫瘤活性初步分析
發(fā)布時間：2018-11-09 12:53
【摘要】：目的:對新型鹵化二型聚酮類抗生素zunyimycins抑菌和抗腫瘤活性進(jìn)行初步分析,為解析其活性機(jī)制提供實(shí)驗(yàn)依據(jù)。方法:(1)通過改變培養(yǎng)基組成、培養(yǎng)時間、培養(yǎng)方式等培養(yǎng)條件,優(yōu)化zunyimycins高產(chǎn)量的培養(yǎng)條件;(2)利用“紙片擴(kuò)散法”測定zunyimycins抑菌能力,“肉湯稀釋法”檢測最低抑菌濃度;(3)利用“MTT”法檢測zunyimycin C對不同來源腫瘤細(xì)胞株的增殖抑制效應(yīng);并通過此方法檢測zunyimycin C與硫辛酸聯(lián)合用藥對Hep G2肝癌細(xì)胞增殖的影響。結(jié)果:(1)在GYM固體培養(yǎng)基的基礎(chǔ)上,添加1%腐殖酸乙醇浸出物,培養(yǎng)時間為17 d,目標(biāo)化合物的產(chǎn)量提高;(2)zunyimycin A對臨床分離菌株MRSA、糞腸球菌、枯草芽孢桿菌等測試菌的最小抑菌濃度分別為6.89μg/m L、16.71μg/m L和3.44μg/m L;zunyimycin B對臨床分離菌株MRSA、糞腸球菌、枯草芽孢桿菌等測試菌的最小抑菌濃度分別為7.88μg/m L、12.81μg/m L和3.94μg/m L;zunyimycin C對臨床分離菌株MRSA、糞腸球菌臨床分離菌株、枯草芽孢桿菌等測試菌的最小抑菌濃度分別為3.75μg/m L、4.07μg/m L和0.938μg/m L;(3)zunyimycin C對Hep G2、Hep1、MKC45、SGC7901、A549、SCAP等細(xì)胞株的24 h半數(shù)抑制濃度分別為13.97μM、22.55μM、21.49μM、44.71μM、27.47μM和18.3μM;(4)8μM的zunyimycin C與硫辛酸聯(lián)合用藥時,可促進(jìn)Hep G2細(xì)胞增殖;16μM和32μM的zunyimycin C與硫辛酸聯(lián)合用藥表現(xiàn)出對Hep G2細(xì)胞增殖抑制效應(yīng)。結(jié)論:(1)在GYM培養(yǎng)基中添加1%的腐殖酸(乙醇浸出物),培養(yǎng)17 d后乙酸乙酯萃取,可提高zunyimycins類抗生素的產(chǎn)量;(2)zunyimycins對MRSA、腸球菌、枯草芽孢桿菌等革蘭氏陽性菌表現(xiàn)出較好的抑制活性,其中zunyimycin C對臨床分離MRSA和腸球菌等表現(xiàn)出較強(qiáng)的殺菌作用,可望用于治療MRSA、VRE等致病菌的感染;(3)zunyimycin C可抑制Hep G2、A549及MKC45等癌細(xì)胞株的增殖,對抗腫瘤新藥的開發(fā)具有重要的意義。
[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.
【學(xué)位授予單位】：遵義醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R96
本文編號：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.
【學(xué)位授予單位】：遵義醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R96
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