土壤来源链霉菌KIB-717抗植物病原真菌活性成分研究

运用中压MCI柱色谱和半制备HPLC等分离手段对云南省腾冲高黎贡山土壤来源链霉菌KIB-717次级代谢产物进行分离纯化,得到3个单体化合物。运用NMR和MS等波谱方法,并参考相关文献,对所得化合物进行结构分析,分别鉴定为β-rubromycin(1)、γ-rubromycin(2)、griseorhodin F(3)。运用滤纸片法测定这三个化合物对植物病原真菌的抑菌活性。抑菌实验首次证明化合物1和2对番茄灰霉病菌(Botrytis cinerea)、稻瘟病病菌[Magnaporthe grisea(Hebert)Barr.]等所测植物病原真菌表现出一定的抑制作用。     

忽地笑内生青霉菌GZWMJZ-39次生代谢产物研究

为获得活性微生物代谢产物,从贵阳忽地笑的鳞茎中分离得到内生真菌GZWMJZ-39,发酵产物经过硅胶柱色谱、凝胶柱色谱和半制备高效液相色谱进行分离纯化,运用NMR、MS等手段鉴定了6个化合物的化学结构,即peniginseng B(1)、peniginseng A(2)、4-(3,4-二羟基苯甲酰氨基)丁酸(3)、4-(3,4-二羟基苯甲酰氨基)丁酸甲酯(4)、peniamidone B(5)、chaetoglobosin G(6),其中化合物1和2首次以单体化合物形式报道。活性测试标明,化合物1~5具有较强的抗氧化活性,其IC50为3.9-27.4μmol/L;化合物1~6具有弱的乙酰胆碱酯酶抑制活性,在50μg/m L的浓度下抑制率在25.2%~32.6%。     

海洋真菌Arthrinium sp. UJNMF0008代谢产物的研究

为丰富海洋真菌的化学多样性,发现海洋真菌活性代谢产物,对海洋沉积物来源真菌Arthriniumsp.UJNMF0008的化学成分及其生物活性进行研究,采用硅胶柱色谱、凝胶柱色谱、反向柱色谱和高效液相色谱等方法从海洋沉积物来源真菌Arthriniumsp.UJNMF0008的发酵提取物中分离到5个化合物,通过核磁共振、质谱等方法,结合文献对照,鉴定了化合物的结构分别为arthoneF(1)、arthoneG(2)、sydoxanthoneC(3)、(3R,4R)-cis-4-hydroxymellein(4)和2-(2′S-hydroxypropyl)-5-methyl-7-hydroxychromone(5),其中化合物1和2是新化合物,化合物3首次从该属真菌中分离到。活性测试显示,化合物1~5在50μmoL/L的测试浓度下均没有表现出明显的抗氧自由基活性、抗菌活性以及NO释放抑制活性。     

青海湖土壤来源链霉菌L8次级代谢产物的分离与鉴定及抑菌活性研究

采用硅胶柱色谱、凝胶柱色谱、半制备HPLC等分离方法对青海湖干旱土壤来源的链霉菌Streptomyces pactum L8的次级代谢产物进行分离纯化,共得到7个化合物。通过NMR、MS等波谱数据分析,对所得化合物进行结构解析,鉴定为Germicidin B(1)、Germicidin A(2)、1-Acetyl-β-carboline(3)、N-Isobutylacetamide(4)、cyclo-(1-Pro-1-Val)(5)、cyclo-(1-Pro-1-Phe)(6)和3-Hydroxy-3-(2-Hydroxyethyl)-6-(3-Methylbut-2-en-1-yl)indolin-2-one(7),其中化合物7为新化合物。初步抑菌活性筛选发现化合物3对金黄色葡萄球菌有微弱的活性,化合物4对玉米弯孢病菌有弱的抑制作用。     

北桑寄生内生真菌的分离及其次级代谢产物分析

首次对药用植物北桑寄生叶片中的内生真菌进行分离纯化,从中筛选出具有较高生物活性的菌株,鉴定此菌株并对其次级代谢产物进行初步分离。采用组织块法分离内生真菌,对其进行抗氧化活性和抑菌活性筛选;通过形态学和分子生物学方法鉴定其种属;运用柱色谱、重结晶等方法分离次级代谢产物,波谱学鉴定其结构。从北桑寄生叶片中分离纯化得到29株内生真菌,检测得到一株具有较高抗氧化和抑菌活性的菌株,鉴定为Alternaria alternata,从该菌次级代谢产物中首次分离得到3个单体化合物,分别为alternariol-5-O-methyl ether(1)、alternariol(2)、cis,cis-9,12-octadecadienoic acid(3)。化合物1和2具有较弱的抗氧化活性,化合物1和3表现出一定的抑菌活性。     

深海真菌Penicillium herquei FS83次生代谢产物研究

利用正相硅胶柱、反相硅胶柱、凝胶柱、薄层层析以及高效液相色谱法等色谱技术从深海真菌Penicillium herquei FS83的液体发酵产物中分离得到5个化合物,通过波谱数据分析结合文献对照,分别鉴定为peniherin A(1)、sclerodin(2)、对羟基苯乙酸甲酯(3)、对羟基苯乙酮(4)、(R)-甲羟戊酸内酯(5)。其中化合物1为新化合物,化合物2为首次从该属真菌中分离得到。生物活性实验显示,化合物1无明显细胞毒活性及抑菌活性。     

春砂仁内生真菌Letendraea helminthicola A696的次级代谢产物研究

研究春砂仁内生真菌Letendraea helminthicola A696的次级代谢产物,采用硅胶柱色谱、ODS反相柱色谱、凝胶柱色谱及高效液相色谱等方法从该菌株的发酵液中分离得到8个化合物,通过理化性质及谱学数据分析,分别鉴定为11-hydroxyl tricinonoic acid(1)、3-(3,5-二叔丁基-4-羟基苯基)丙酸甲酯(2)、gibepyrone F(3)、gibepyrone D(4)、对羟基苯甲醛(5)、对甲氧基苯乙酸(6)、间羟基苯乙酸(7)、麦角甾醇(8),其中化合物1为新化合物,化合物2～8均为首次从Letendraea属真菌中分离得到。选取化合物1～5进行了抗菌和抗肿瘤活性试验,结果表明化合物1～5在100μg/mL浓度下均无抗菌和抗肿瘤活性。     

海洋真菌Aspergillus jensenii SS5中化学成分研究

利用多种柱色谱分离技术从海洋真菌Aspergillus jensenii SS5的液体发酵产物中分离获得4个已知化合物,并通过NMR、HR-ESI-MS、X单晶衍射等技术鉴定了它们的结构,分别是epigriseofulvin(1)、sterigmatocystin(2)、brevianamide M(3)、meleagrin(4),其中化合物1～3是首次从曲霉属真菌A.jensenii中分离获得。采用SRB法对分离获得的天然产物进行体外细胞毒性测试,结果表明化合物4对人肺癌A549细胞和人肝癌Bel-7402细胞均有较好抑制作用,化合物2对A549人肺癌细胞株有较好抑制作用。本研究作为海洋真菌A.jensenii SS5的化学成分的补充研究,发现了2个具有较好细胞毒活性的化合物,为曲霉属海洋真菌活性天然产物的开发提供了理论依据。     

土壤真菌Curvularia affinis HS-FG-196抗肿瘤化学成分的再研究

为对土壤真菌Curvularia affinis HS-FG-196的次级代谢产物及其体外抗肿瘤活性进行进一步研究。实验采用大孔吸附树脂HP-20树脂柱、硅胶柱、凝胶LH-20柱及半制备高效液相色谱柱从Curvularia affinis HS-FG-196的发酵培养物中分离得到六个单体化合物(1～6)。利用~1H NMR、¹³C NMR、~1H-~1H COSY、HMQC、HMBC、IR、UV和MS等波谱分析方法对其进行了结构鉴定,分别是:pyrenocine S (1)、pyrenocine B (2)、pyrenocine E (3)、pyrenocine I (4)、pyrenochaetic acid B (5)和pyrenochaetic acid C (6),其中化合物1是新化合物。对所得单体化合物进行了体外抗肿瘤活性测试,结果显示化合物1、2、3对肿瘤细胞A549、HCT-116、ACHN、K562和HepG2表现出较强的活性。     

链霉菌Streptomyces sp.KIB-H1424中的一个新的烷基间苯二酚类化合物

运用色谱学方法对一株来自云南省玉溪市元江县的土壤链霉菌Streptomyces sp.KIB-H1424的次级代谢产物进行分离纯化,得到6个单体化合物。运用NMR、MS及与文献数据对比等手段,确定其为一系列的烷基间苯二酚类似物,其中包括1个新的烷基间苯二酚类化合物Adiposatatin E(1)以及5个已知的烷基间苯二酚类似物Adipostatin A(2)、Adiposatin B(3)、Adipostatin C(4)、Adipostatin D(5)和5-Heptadecyl-1,3-benzenediol(6)。运用滤纸片法测定6个化合物对几种病原细菌和真菌的抑菌活性,发现化合物1~6不具有显著的抑菌活性。     

In-vitro inhibitory activities of 2 new orally absorbable imidazole derivatives: BAY n 7133 and BAY 1 9139

The inhibitory activities of 2 new orally absorbed antifungal imidazole derivatives, BAY n 7133 and BAY 1 9139, were compared in vitro with those of ketoconazole and miconazole. Clinical isolates of pathogenic fungi tested included 35 yeasts, 62 dimorphic fungal pathogens, 37 filamentous fungi and 31 dermatophytes. LY 121019, a semisynthetic analog of echinocandin B, was included in tests with the pathogenic yeasts. Both BAY n 7133 and BAY 1 9139 were found to be broad spectrum antifungal agents. The spectra of these newer compounds were comparable to those of ketoconazole and miconazole; however only BAY n 7133 resembled these latter 2 imidazoles quantitatively in terms of the degree of antifungal activity as indicated by measurable MICs. In contrast, the spectrum of LY 121019 appeared to be confirmed only to isolates of Candida.     

Evaluation of cytotoxic,antifungal, and larvicidal activities of different bis-sulfonamide Schiff base compounds

Schiff bases (imines or azomethines) are versatile ligands synthesized from the condensation of amino compounds with active carbonyl groups and used for many pharmaceutical and medicinal applications. In our study, we aimed to determine the cytotoxic, antifungal and larvicidal activities of biologically potent bis-sulfonamide Schiff base derivatives that were re-synthesized by us. For this aim, 16 compounds were re-synthesized and tested for their cytotoxic, antifungal and larvicidal properties. Among this series, compounds A1B2 , A1B4 , A4B2 , A4B3 , and A4B4 were shown to have cytotoxic activity against tested cancer lung cell line (A549). The most potent antifungal activity was observed in compounds A2B1 and A2B2 against all fungi. A1B1 showed the strongest larvicidal effect at all concentrations at the 72nd h (100% mortality). These obtained results demonstrate that these type of bis-substituted compounds might be used as biologically potent pharmacophores against different types of diseases.     

Design,synthesis, and biological evaluation of novel 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted benzylamino-2-propanols

Based on the results of computational docking to the active site of the cytochrome P450 14α-demethylase (CYP51), a series of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted benzylamino-2-propanols as analogs of fluconazole were designed, synthesized, and evaluated as antifungal agents. Results of preliminary antifungal tests against eight human pathogenic fungi in vitro showed that all the title compounds exhibited excellent activities with broad spectrum.     

飞机草地上部分化学成分及其抑菌活性研究

为探究飞机草地上部分化学成分及其抑菌作用.采用正相硅胶、Sephadex LH-20等色谱方法,从飞机草乙酸乙酯提取物中得到10个化合物,根据1H NMR、13C NMR、MS波谱数据,分别鉴定为:5,6,7,4'-四甲氧基黄烷酮(1)、圣草素-7,4'-二甲醚(2)、5,7-二羟基-6,4'-二甲氧基黄酮(3)、二氢...     

Synthesis and SAR studies of biaryloxy-substituted triazoles as antifungal agents

A series of 1-(substituted biaryloxy)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl) propan-2-ol were synthesized and their antifungal activities were evaluated against eight human pathogenic fungi in vitro. Seventeen compounds showed activity 4- to 64-fold higher than voriconazole against Candida albicans. SAR clearly suggested that introduction of a biaryloxy side chain greatly enhanced the antifungal activity of triazole analogs against Candida species.     

Anti-Candida metabolites from endophytic fungi

Submerged cultures of some 1500 Ascomycota and Basidiomycota isolated from their fruit-bodies or as soil-borne, coprophilous or endophytic fungi were screened for activity against Candida albicans and a range of other pathogenic and saprotrophic fungi. Considerably more Ascomycota (11-16%) than Basidiomycota (3.5%) produced metabolites with activity against C. albicans. From five species of endophytes, six bioactive compounds were isolated and identified, viz. cerulenin (1), arundifungin (2), sphaeropsidin A (3), 5-(1,3-butadiene-1-yl)-3-(propene-1-yl)-2-(5H)-furanone (4), ascosteroside A (formerly called ascosteroside; 5) and a derivative of 5, ascosteroside B (6). 1, 3 and 5 were isolated from fungi belonging to different orders than previously described producers. Antifungal activities of 2 and 4-6 in the agar diffusion test were comparable with those of amphotericin B. Compound 6 exhibited a similar antifungal activity as 5 but its cytotoxicity towards Hep G2 cells was considerably lower. This study points to endophytic fungi related to hemibiotrophic or latent plant pathogens as an important source of bio- and chemodiversity.     

1‐Phenyl‐3‐pentanone,a Volatile Compound from the Edible Mushroom Mycoleptodonoides aitchisonii Active Against Some Phytopathogenic Fungi

Volatiles produced by mycelia of mushrooms with aromatic odour were investigated for their antifungal activity against plant‐pathogenic fungi. The results of the screening of 23 species of basidiomycetes revealed that volatile substances from mycelia of Mycoleptodonoides aitchisonii (TUFC10099), an edible mushroom, strongly inhibited the mycelial growth, spore germination and lesion formation on host leaves of some plant‐pathogenic fungi including Alternaria alternata, A. brassicicola, A. brassicae, Colletotrichum orbiculare and Corynespora cassiicola. The volatile compounds were isolated from the culture filtrate of M. aitchisonii, and 1‐phenyl‐3‐pentanone was identified as a major antifungal volatile. The compound had significantly inhibitory activity against plant‐pathogenic fungi at 35 ppm. This is the first report that the volatile compound produced by mycelia of M. aitchisonii has antifungal activity against plant‐pathogenic fungi.     

Design, synthesis, and antifungal activities of novel 1H-triazole derivatives based on the structure of the active site of fungal lanosterol 14 alpha-demethylase (CYP51)

A series of fluconazole (1) analogues, compounds 3a-k, were prepared as potential antifungal agents. They were designed by computational docking experiments to the active site of the cytochrome P450 14alpha-sterol demethylase (CYP51), whose crystal structure is known. Preliminary biological tests showed that most of the target compounds exhibit significant activities against the eight most-common pathogenic fungi. Thereby, the most potent congener, 1-[(4-tert-butylbenzyl)(cyclopropyl)amino]-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol (3j), was found to exhibit a broad antifungal spectrum, being more active against Candida albicans, Candida tropicalis, Cryptococcus neoformans, Microsporum canis, and Trichophyton rubrum (MIC80 < 0.125 microg/ml) than the standard clinical drug itraconazole (2). The observed affinities of the lead molecules towards CYP51 indicate that a cyclopropyl residue enhances binding to the target enzyme. Our results may provide some guidance for the development of novel triazole-based antifungal lead structures.     

New azoles with antifungal activity: Design, synthesis, and molecular docking

In order to search for many target compounds with excellent activities, a series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluoro-phenyl)-3-[(4-substituted phenyl)-piperazin-1-yl]-propan-2-ols were designed, synthesized, and evaluated as antifungal agents. Results of preliminary antifungal tests against eight human pathogenic fungi in vitro showed that all the title compounds exhibited excellent activities with broad spectrum. Moreover, a molecular model for the binding between 5a and the active site of CACYP51 was provided based on the computational docking results.     

New triazole derivatives as antifungal agents: synthesis via click reaction, in vitro evaluation and molecular docking studies

A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols (5a-5y) which are analogues of fluconazole, have been designed and synthesized via Cu(I)-catalyzed azide-alkyne cycloaddition on the basis of computational docking experiments to the active site of the cytochrome P450 14α-demethylase (CYP51). The in vitro antifungal activities of all the target compounds were evaluated against eight human pathogenic fungi. Compound 5l showed the best antifungal activities.