三株真菌Cosmospora joca、Xylotumulus gibbisporus及Thelonectria coronalis之活性成分研究

Bioactive constituents from Cosmospora joca, Xylotumulus gibbisporus and Thelonectria coronalis

張雅植(Ya-Chih Chang)

指導教授 ： 李慶國

共同指導教授 ： 李宗徽(Tzong-Huei Lee)

臺北醫學大學/藥學院/藥學系(碩博士班)/博士(2016年)

摘要

本研究之初始利用抑制一氧化氮合成酶或抑制癌細胞生長的活性分析平台來篩選真菌培養株，以篩檢出具有抗發炎活性或細胞毒性的真菌株，發現某些真菌株的醱酵培養液對於抑制RAW264.7細胞之一氧化氮的產生或非小細胞肺癌A549細胞具有毒殺作用，而後選定Cosmospora joca YMJ 89041201、Xylotumulus gibbisporus YMJ 863 及Thelonectria coronalis YMJ 94043006三株真菌進行其活性成分研究。接著以麥芽萃取物 (malt extract) 為培養基加以擴大培養，針對醱酵液所含代謝產物進行分析、分離與純化，計獲得23個化合物，分別為：cosmosporasides A E (1 5)、sordarins C F (6 9)、xylogiblactones A C (10 12)、sordarin (13)、hypoxylactone (14)、5-methylmellein (15)、cylindrol B (16)、LL-Z1272  (17)、chloronectrin (18)、ilicicolin F (19)、colletorin B (20)、ilicicolin D (21)、ilicicolin C (22) 及colletochlorin B (23)，其中倍半萜糖苷化合物1 5、二萜糖苷化合物6 9及聚酮化合物10 12為新化合物。在抗菌活性試驗顯示，化合物13對於兩株白色念珠菌 (Candida albicans) ATCC 18804和ATCC MYA-2876及酵母菌 (Saccharomyces cerevisiae) ATCC 2345具有中度的抑菌效果，最小抑菌濃度分別為64、32及32 μg/mL；化合物16 23對於RAW264.7 細胞產生之一氧化氮具有顯著的抑制活性，其中化合物19和21的活性最顯著，其IC50 分別為6.59 及9.43 μM；此外，化合物19與21 23對於非小細胞肺癌A549細胞具有顯著的毒殺活性，其GI50 分別為1.2、1.1、8.2 及4.5 μM。

關鍵字

Cosmospora joca、Xylotumulus gibbisporus、Thelonectria coronalis、一氧化氮、抗菌活性、細胞毒性、cosmosporaside、sordarin、xylogiblactone

並列摘要

The ethyl acetate extracts of the fermented broths of Cosmospora joca YMJ 89041201, Xylotumulus gibbisporus YMJ 863 and Thelonectria coronalis YMJ94043006 were found to exhibit significant NO production inhibitory or growth inhibitory activity against A549 lung cancer cell line in our preliminary screening. Therefore, bioassay-guided fraction and separation of the active component from these three broths were carried out resulting in the isolation of twenty-three compounds. Their structures were elucidated to be cosmosporaside A (1), cosmosporaside B (2), cosmosporaside C (3), cosmosporaside D (4), cosmosporaside E (5), sordarin C (6), sordarin D (7), sordarin E (8), sordarin F (9), xylogiblactone A (10), xylogiblactone B (11), xylogiblactone C (12), sordarin (13), hypoxylactone (14), 5-methylmellein (15), cylindrol B (16), LL-Z1272  (17), chloronectrin (18), ilicicolin F (19), colletorin B (20), ilicicolin D (21), ilicicolin C (22) and colletochlorin B (23). Of these compounds identified, five novel sesquiterpene glycosides 1 5, four new tetracyclic diterpene glycosides 6–9 and three new polyketides 10 12 were novel chemical entities. Compound 13 exhibited moderate antimicrobial activities against two strains Candida albicans ATCC 18804, MYA-2876 and Saccharomyces cerevisiae ATCC 2345 with MIC values of 64, 32 and 32 μg/mL, respectively. Compounds 16–23 exhibited significant inhibitory activities on NO production of RAW264.7 cells induced by lipopolysaccharide. Both 19 and 21 exert significant inhibitory activities on NO production with IC50 values of 6.59 and 9.43 μM, respectively. In addition, 19 and 21 23 exhibited significant growth inhibitory activities against A549 cell line with GI50 values of 1.2, 1.1, 8.2 and 4.5 μM, respectively.

並列關鍵字

Cosmospora joca ； Xylotumulus gibbisporus ； Thelonectria coronalis ； cytotoxicity ； antimicrobial activity ； Nitric oxide ； cosmosporaside ； sordarin ； xylogiblactone

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