红树植物角果木内生真菌J62生物活性成分研究

目的 研究红树植物角果木内生真菌J62产生的活性次生代谢产物。方法 采用多种柱色谱技术进行分离纯化,根据理化常数和波谱数据鉴定化合物的结构,采用滤纸片琼脂扩散法测定化合物抗金黄色葡萄球菌(Staphylococcus aureus)和白色念珠菌(Candida albicans)活性,利用MTT法测定各化合物的体外细胞毒活性。 结果 从角果木内生真菌J62发酵液中分离鉴定了10个化合物,分别为：反式桂皮酸 (1),3,4-二甲氧基苯甲醇 (2), 2-[(3,4-dimethoxyphenyl)methyl]-4,5-dimethoxy-benzenemethanol (3), l尿嘧啶核苷(4), similin B (5),coibanol C (6), hymatoxin C (7), 5,8-epidioxy-5a,8a-ergosta-6,22E-dien-3b-ol (8),豆甾-7,22-二烯-3b,5a,6a-三醇 (9)和crispin A (10)。结论 生物活性测试结果表明,化合物1, 2和7具有抗金黄色葡萄球菌活性,化合物1和2具有抗白色念珠菌的活性;化合物2和5对肿瘤细胞株K-562显示有生长抑制活性。     

海绵共附生疣孢菌FIM060022抑菌活性代谢产物的研究

目的 从海绵共附生疣孢菌FIM060022的发酵液中分离抑菌活性次级代谢产物.方法 采用多种色谱技术分离纯化获得活性化合物,并对化合物进行结构鉴定及活性测定.结果 从菌株FIM060022的乙酸乙酯提取物中分离得到6个化合物,根据化合物的光谱特征(ESI-MS、1D-NMR和2D-NMR)和理化性质分别鉴定为abyssomicin B(5)、C(1)、H(6),proximicin A(4),lumichrome(2)和腺嘌呤核苷(3).抗菌活性表明化合物1、3～6对藤黄微球菌的生长均有明显的抑制作用.化合物1还对金黄色葡萄球菌的生长有较强的抑制作用,而对枯草芽孢杆菌和短小芽孢杆菌生长的抑制作用相对较弱.此外,化合物4和5对黑曲霉生长具有较弱的抑制作用.结论 本研究从海绵共附生疣孢菌FIM060022中同时分离得到抗菌活性物质abyssomicin和porximicin,化合物2和3为首次从该属菌的代谢产物中分离得到,为进一步开发利用海洋稀有放线菌资源奠定了一定的基础.     

海洋曲霉属真菌菌株F5抑菌活性代谢产物的分离与鉴定

目的 从一株分离自广东湛江特呈岛木榄根际土壤的曲霉属真菌F5的发酵液中分离抑菌活性次级代谢产物.方法 发酵液经乙酸乙酯萃取、正相硅胶柱层析、分子筛层析、C18柱制备色谱分离获得单体,并对化合物进行结构鉴定及活性测试.结果 从菌株F5的乙酸乙酯提取物中分离得到2个内酯、2个异香豆素类化合物和1个不饱和酸,根据化合物的谱学特征(ESI-MS、1H-NMR和13C-NMR)和理化性质分别鉴定为(1)asperlactone、(2)aspyrone、(3)penicillic acid、(4)cis-4-hydro xymellein和(5)trans-4-hydroxymellein.其中化合物4在终浓度50μg/mL时,对Candida albicans有抑制作用.结论 菌株F5分泌的代谢产物cis-4-hydroxymellein(4)对Candida albicans有明显抑制作用.     

海南龙血树内生真菌A12中的抗菌活性成分研究

目的研究海南龙血树内生真菌A12的活性次生代谢产物。方法采用多种柱色谱技术进行分离纯化,根据波谱数据和理化性质鉴定化合物的结构,采用滤纸片琼脂扩散法测定化合物抗金黄色葡萄球菌(Staphylococcus aureus)和耐甲氧西林金黄色葡萄球菌(MRSA)的活性。结果分离鉴定了7个化合物,分别为胞嘧啶核苷(1),尿嘧啶核苷(2),对羟基苯乙酸(3),对羟基苯乙醇(4),尿嘧啶(5),desacetylaustin(6)和thiomethisosildenafil(7)。结论活性测试结果表明化合物3和4具有抗金黄色葡萄球菌和MRSA的活性,首次发现化合物7具有抗金黄色葡萄球菌活性。     

海洋真菌095407的抗菌活性代谢产物的研究

目的对海洋真菌095407的抗菌活性成分进行研究。方法用多种色谱技术对化合物进行分离纯化，用光谱技术和理化性质鉴定化合物的结构，并用滤纸片琼脂扩散法测定化合物的抗耐甲氧西林金黄色葡萄球菌和白色念珠菌活性。结果从095407号真菌发酵液提取物中分离得到4个化合物，分别鉴定为3，4，5-三甲基-1，2-苯二酚（1）、decarboxydihydrocitrinone（2）、甘露醇（3）、刺芒柄花素（4）。结论化合物1为首次以天然产物的形式分离得到，活性测试结果表明化合物1和2具有抗耐甲氧西林金黄色葡萄球菌活性。     

海洋来源真菌Penicillium sp. wqh-572的次级代谢产物研究?

目的 研究浙江普陀岛海泥来源真菌Penicillium sp. wqh-572的次级代谢产物及其抑菌活性。方法 将菌株进行大规模发酵,乙酸乙酯萃取,采用小孔树脂MCI柱和半制备型高效液相色谱等分离纯化方法,通过核磁(₁H NMR和₁₃C NMR)和质谱(MS)等波谱分析方法,并与相关文献比较,鉴定化合物结构。结果 从该真菌发酵液的乙酸乙酯萃取相中分离得到6个化合物,鉴定结果分别为physcion (1)、emodin (2)、7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (3)、isorhodoptilometrin (4)、2-(2’, 4’, 6’-trihydroxyphenyc)-(7-hydroxy-5-methyc) chromone (5)及(Z)-N-(4-hydroxy styryl) formamide (6)。其中,其中化合物5为首次从青霉属真菌中分离得到。化合物1对3种植物病原菌均具有抑制作用。     

红海榄内生真菌AGR12及其抑菌活性代谢产物

目的 鉴定一株分离自海南文昌红海榄茎的内生真菌菌株AGRl2,分离和鉴定其抑菌活性代谢产物.方法 根据菌株的形态学特征和ITS序列鉴定菌株AGR12.通过硅胶柱层析、Sephadex LH-20凝胶柱层析、制备薄层层析及重结晶等方法分离纯化代谢产物,并根据它们的紫外、质谱、氢谱和碳谱等光谱数据确定化合物结构.结果 菌株AGRl2被鉴定为镰孢霉属木贼镰刀菌(Fusarium equiseti),其在优化后的GMPY培养基中28℃、160r/min振荡培养7d后获得的发酵液具有明显的抑菌活性.从发酵液及菌体中共分离到3个化合物,鉴定为equisetin、epi-equisetin和麦角甾醇(ergosterol),其中equisetin对枯草芽孢杆菌和金黄色葡萄球菌的生长具有明显的抑制活性,最低抑菌浓度(MIC)均为32Bg/mL;epi-equisetin对枯草芽孢杆菌的生长也具有明显的抑制作用,MIC为32μg/mL.结论 木贼镰刀菌菌株AGRl2为首次从红树植物中分离到的内生真菌,其分泌的代谢产物equisetin和epi-equisetin具有明显的抑菌活性.     

海洋真菌烟曲霉Aspergillus fumigatus YK-7次级代谢产物的分离鉴定及抗肿瘤活性

目的研究海洋真菌烟曲霉Aspergillus fumigatus YK-7次级代谢产物,以期获得活性先导化合物。方法采用硅胶柱色谱、ODS柱色谱、凝胶柱色谱、高效液相色谱等方法进行分离纯化,通过理化性质和波谱数据分析鉴定化合物的结构。采用台盼蓝法和MTT法进行抗肿瘤活性测试。结果从烟曲霉的真菌发酵液的乙酸乙酯萃取物和菌丝体的丙酮提取物中分离得到10个生物碱类化合物,分别鉴定为chaetominine(1)、(-)-11-epi-chaetominine(2)、fumiquinazoline A(3)、fumiquinazoline B(4)、fumiquinazoline C(5)、fumiquinazoline F(6)、fumiquinazoline G(7)、fumiquinazoline J(8)、bis-N-norgliovictin(9)、2-methylthio-cyclo(Phe-Ser)(10)。体外抗肿瘤活性测试结果显示,化合物3、6、7、8对人单核细胞白血病细胞(U937)的IC50值分别为87.1、16.4、33.3、8.6μmol·L~(-1);化合物8对人前列腺癌细胞(PC-3)的IC50值为58.5μmol·L~(-1)。结论化合物1、2为首次从海洋来源烟曲霉中分离得到。化合物3、6、7、8对选定的人肿瘤细胞U937和PC-3具有一定的体外抗增殖活性。     

海洋放线菌活性组分AM105-Ⅱ的分离与结构鉴定

目的对海洋来源的放线菌AM105发酵液中抗MRSA活性物质进行分离和鉴定。方法运用硅胶柱层析、制备薄层层析和Sephadex LH20柱层析从菌株发酵液中进行活性追踪分离,通过现代波谱数据分析进行化学结构鉴定,并采用MIC评价其生物活性。结果与结论从发酵液中分离得到活性组分AM105-Ⅰ,鉴定其属于利福霉素类抗生素,由rifamycin S及其异构体isorifamycin S组成。经检索,isorifamycin S是一种新结构的化合物。MIC结果反映isorifamycin S抑菌活性明显优于目前临床药物rifamycin SV。     

海洋细菌Bacillus coagulans spp.heishijiaosis 发酵液抗真菌活性及其机制研究

目的对凝结芽胞杆菌黑石礁新亚种LU-B02产生的抗白色念珠菌活性物质的作用靶位及抑菌谱进行了研究。方法采用山梨醇保护形态变异法结合扫描电镜超微结构观察研究了活性物质的作用靶位,最小抑菌浓度(MIC)法比较了该菌发酵液对不同真菌的抑菌活性。结果该活性物质抑制白色念珠菌细胞壁中的主要组分——葡聚糖的合成从而造成其细胞壁残缺。该活性物质具有抗真菌专一性,对革兰氏阳性代表菌金黄色葡萄球菌和革兰氏阴性代表菌大肠杆菌等细菌均无抑制效果,而对人体病原真菌抑菌效果较为明显,尤其是对白色念珠菌的抑制效果较好。MIC测定表明白色念珠菌对LU-B02活性物质高度敏感,相当于斯皮仁诺8~16μg,抑菌效价每毫升相当于3 500 U制霉菌素或洁尔阴活性的4倍。发酵液在酸性条件下加入0.2%冰片时,室温下存放6个月仍可保持良好的抗白色念珠菌活性。结论凝结芽孢杆菌黑石礁新亚种(Bacillus coagulans spp.heishijiaosis)产生的活性物质在控制以白色念珠菌为主的真菌感染方面具有良好应用前景。     

Studies of Antimicrobial Activities of some 4-Thiazolidinone Fused Pyrimidines, [1,5]-Benzodiazepines and their Oxygen Substituted Hydroxylamine Derivatives

Thiazolidin-4-one fused pyrimidines, [1,5]-benzodiazepines and their oxygen substituted hydroxylamine derivatives have been screened for antibacterial, antifungal and antimalarial activity. Bacillus subtilis, Escherichia coli, Proteus mirabilis and Salmonella typhi were used for antibacterial screening. Aspergillus fumigatus and Candida albicans were used for antifungal screening and Plasmodium species were used for antimalarial screening. The antibacterial and antifungal activities are expressed in terms of zone of inhibition and antimalarial activity is expressed in IC(50) value. Fifteen compounds 2Xa, 2Xb, 2Xc, 2Xs, 3IV, 3Va, 3Vc, 3VIIIa, 3VIIIh, 3IXa, 3IXb, 3IXc, 3Xa, 4IXa and 4Xa were tested for antibacterial as well as antifungal activity and seven compounds 2IXb, 2Xb, 3VIIIc, 3Xc, 4IXa, 4Xa and 4IXw were tested for antimalarial activity. Streptomycin, griseofulvin and chloroquine were taken as standard drugs in antibacterial, antifungal and antimalarial activity, respectively. The compound 2Xs was found significant antimicrobial against Bacillus subtilis, E. coli, Aspergillus fumigatus and Candida albicans as well as compound 3Xa was significant antimicrobial against Bacillus subtilis, E. coli, Salmonella typhi, Aspergillus fumigatus and Candida albicans. The compound 2Xb showed significant antimalarial activity.     

A new nonadride derivative, dihydroepiheveadride, as characteristic antifungal agent against filamentous fungi, isolated from unidentified fungus IFM 52672

In the screening of searching for new antifungal agents, a new nonaride compound, dihydroepiheveadride (1), was isolated from unidentified fungus IFM 52672 as the most potent antifungal principle from this organism. The structure of 1 was established on the basis of spectroscopic and chemical investigation, as well as detailed comparison of the spectroscopic and physico-chemical data of the oxidized derivative (3) from 1 with those of heveadride (2). Compound 1 showed strong antifungal activity against various filamentous fungi including human pathogens Aspergillus fumigatus, Penicillium marneffei and Trichophyton spp. It also showed the growth inhibition activity against certain human pathogenic yeasts such as Trichosporon species, while it had weak or no antifungal activity against Candida spp. and Cryptococcus neoformans, and no antibacterial activity against Bacillus subtilis nor against Escherichia coli. The antifungal potencies of compounds 2 and 3 were found to be weaker than that of 1.     

PF1163A and B, new antifungal antibiotics produced by Penicillium sp. I. Taxonomy of producing strain, fermentation, isolation and biological activities

Two novel antifungal antibiotics, PF1163A and B, were isolated from the fermentation broth of Penicillium sp. They were purified from the solid cultures of rice media using ethyl acetate extraction, silica gel and Sephadex LH-20 column chromatographies. PF1163A and B showed potent growth inhibitory activity against pathogenic fungal strain Candida albicans but did not show cytotoxic activity against mammalian cells. These compounds inhibited the ergosterol biosynthesis in Candida albicans.     

New cyclic depsipeptide antibiotics, clavariopsins A and B, produced by an aquatic hyphomycetes, Clavariopsis aquatica. 1. Taxonomy, fermentation, isolation, and biological properties

Clavariopsins were isolated from the fermentation broth of Clavariopsis aquatica AJ 117363. Clavariopsins are cyclic depsipeptide antibiotics with the molecular weight of 1,153 and 1,139. Clavariopsins showed in vitro antifungal activity against not only Aspergillus fumigatus but also, although to a lesser extent, A. niger and Candida albicans.     

Synthesis and in-vitro antifungal activity of 6-substituted-phenyl-2- {[(4'-substituted phenyl-5'-thioxo)-1,2,4-triazol-3-yl]-methyl}-2,3,4,5-tetrahydropyridazin-3-one derivatives

The synthetic pathway for 6-substituted phenyl-2-[{(4'-substituted phenyl-5'-thioxo)-1,2,4-triazol-3-yl}-methyl]-2,3,4,5-tetrahydropyridazin-3-one compounds was achieved by a sequence of reactions starting from respective aryl hydrocarbons and is illustrated in Scheme 1. All the compounds were tested for their in vitro antifungal activity on five fungal species, namely Candida albicans, Trichophyton rubrum, Aspergillus flavus, Aspergillus niger and Penicillium citrinium. The chloro substituent derivative (compound 5g) showed the highest activity against all the fungal species. The MIC of the standard drug voriconazole was between 0.10 - 0.40 microg/mL against all the fungal species except A. fumigatus. The two electronegative groups of Cl were increasing the activity of 1,2,4-triazole. As we increased the bulky group or aromatic group on benzene ring, there was a decrease of activity as in case of compound 1.     

Synthesis of 4-hydroxycoumarin heteroarylhybrids as potential antimicrobial agents

A new series of 4-hydroxycoumarin derivatives 3a-d was synthesized by the reaction of 3-bromo-4-hydroxy coumarin 1 with various heteroaldehydes 2a-d in good yields. The synthesized compounds were characterized on the basis of their elemental and spectral (IR, (1)H-NMR and mass spectrometry) analysis. All target compounds were evaluated for their in-vitro antimicrobial activity against Streptococcus pyogenes, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, and Escherichia coli bacterial strains and fungal cultures of Candida albicans, Aspergillus fumigatus, Trichophyton mentagrophytes, and Penicillium marneffei by disk diffusion assay with slight modifications. The minimum inhibitory concentration (MIC) was determined for the test compounds as well as for reference standards. Among the tested compounds, 3a has shown the most potent antibacterial as well as antifungal activities.     

Yatakemycin,a novel antifungal antibiotic produced by Streptomyces sp. TP-A0356

In the screening of novel antifungal compounds, yatakemycin was found in the culture broth of Streptomyces sp. TP-A0356. Yatakemycin was obtained by solvent extraction of the fermentation broth and chromatographic purification using ODS column and preparative HPLC. The structure of yatakemycin was elucidated by NMR and CID-MS/MS experiments as a novel antibiotic belonging to a family of CC-1065 and duocarmycins known to be DNA alkylating agents. Yatakemycin inhibited the growth of pathogenic fungi such as Aspergillus fumigatus and Candida albicans with the MIC values of 0.01-0.03 microg/ml, more potent than amphotericin B (MIC: 0.1-0.5 microg/ml) or itraconazole (MIC: 0.03-0.2 microg/ml). It also showed potent cytotoxicity against cancer cell lines with the IC50 of 0.01-0.3 microg/ml.     

FR171456, a novel cholesterol synthesis inhibitor produced by Sporormiella minima No. 15604. I. Taxonomy, fermentation, isolation, physico-chemical properties

FR171456 and FR173945, novel and potent cholesterol synthesis inhibitors, have been isolated from the fermentation broth of a fungal strain No. 15604. This strain was identified Sporormiella minima from its mycological characteristics. FR171456 and FR173945 strongly inhibited cholesterol synthesis in human hepatoma cell line Hep G2. These compounds also have in vitro antifungal activity against Candida albicans and Aspergillus fumigatus.     

FR220897 and FR220899, novel antifungal lipopeptides from Coleophoma empetri no. 14573

Novel antifungal lipopeptides, FR220897 and FR220899, were isolated from the fermentation broth of a fungal strain No. 14573. This strain was identified as Coleophoma empetri No. 14573 from morphological and physiological characteristics. FR220897 and FR220899 showed antifungal activities against Aspergillus fumigatus and Candida albicans attributed to inhibition of 1,3-beta-glucan synthesis. Furthermore, FR220897 was effective in a murine model of systemic candidiasis.     

Polyketides from the fungus Penicillium decumbens

Two new polyketides, 3,11-dihydroxy-6,8-dimethyldodecanoic acid (1) and trichopyrone B (2), together with two known polyketides, sorbicillin (3) and penicillone A (4), have been isolated from the cultures broth of the fungus Penicillium decumbens. Their structures were elucidated by extensive spectroscopic analysis. All isolated compounds were evaluated for their antibacterial and cytotoxic activities. Of these, compound 3 showed antifungal activity toward Candida albicans Y0109 with a MIC value of 50 μM. Moreover, compounds 3 and 4 exhibited selective cytotoxicity against the human hepatocellular carcinoma (QGY-7703) cell line with the IC₅₀ values of 32.5 and 22.8 μM, respectively.