臺灣株真菌Nalanthamala psidii YMJ400、Trichobotrys effusa YMJ1179 及Alveophoma caballeroi YMJ309 醱酵液成分之研究

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Title:	臺灣株真菌Nalanthamala psidii YMJ400、Trichobotrys effusa YMJ1179 及Alveophoma caballeroi YMJ309 醱酵液成分之研究 Chemical constituents from the fermented broths of Nalanthamala psidii YMJ400, Trichobotrys effusa YMJ1179 and Alveophoma caballeroi YMJ309 isolated in Taiwan
Authors:	蕭惠勻 Hsiao, Hui-Yun
Contributors:	生藥學研究所李宗徽
Keywords:	Nalanthamala psidii;Trichobotrys effusa;Alveophoma caballeroi;細胞毒性;抗菌活性;一氧化氮生成 Nalanthamala psidii;Trichobotrys effusa;Alveophoma caballeroi;cytotoxicity;antimicrobial activity;NO production
Date:	2012-07-07
Issue Date:	2018-10-04 17:31:39 (UTC+8)
Abstract:	利用抑制肺癌細胞 (A549) 生長及抑制一氧化氮合成酶的活性分析平台來篩選真菌培養株，以篩檢出具有細胞毒性或抗發炎活性的真菌株，發現某些真菌株的醱酵培養液對於肺癌細胞具有毒殺作用，或抑制RAW264.7 細胞之一氧化氮的產生，而後選定Nalanthamala psidii YMJ400、Trichobotrys effusa YMJ1179 及Alveophoma caballeroi YMJ309 三株真菌進行其成分研究。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17 個化合物，分別為：myxosporsidol A (1)、trichodermin (2)、myxosporsidol B (3)、O-methyldihydrobotrydial (4)、2,5-di(hydroxymethyl)furan (5)、trichophenol A (6)、trichophenol B (7)、trichophenol C (8)、trichophenol D (9)、coriloxin (10)、zythiostromic acid A (11)、radicicol (12)、3,5-dihydroxytoluene (13)、5-(hydroxymethyl)furfural (14)、alveophomic acid (15)、α-acetylorcinol (16) 及curvulinic acid (17)，其中倍半萜類化合物1、酚類化合物6–9 及酸類化合物15為新化合物。在活性試驗上，化合物2 對於肺癌細胞、口腔癌細胞 (Ca9-22)、抗藥性卵巢癌細胞 (TOV-21G-Tx) 及多重抗藥性癌細胞 (NCI/ADR-RES) 具有顯著的抑制活性，其GI50 分別為0.67、0.48、0.28 及0.35 μM，化合物12 對肺癌細胞、抗藥性卵巢癌細胞、大腸癌細胞 (HT-29) 及肝癌細胞 (SK-Hep-1) 也有顯著的抑制活性，其GI50 分別為1.43、0.68、0.95 及9.67 μM，化合物6–9 對於肺癌細胞皆具有中度抑制活性，其GI50 分別為25.61、19.32、16.19 及24.31 μM，抗菌活性試驗顯示，化合物2 對白色念珠菌 (Candida albicans)、新型隱球菌 (Cryptococcus neoformans) 及酵母菌 (Saccharomyces cerevisiae) 皆有顯著的抑菌效果，MIC 分別為2、1 及1 μg/mL，而化合物12 對此三株真菌皆有中度的抑菌效果，MIC 分別為32、16 及32 μg/mL，此外，化合物1 對於RAW264.7 細胞產生之一氧化氮具有輕微的抑制作用，其IC50 為74.63 μM。 The ethyl acetate extracts of the fermented broths of Nalanthamala psidii YMJ400, Trichobotrys effusa YMJ1179 and Alveophoma caballeroi YMJ309 were found to exhibit significant growth inhibitory activity against A549 lung cancer cell line or NO production inhibitory in our preliminary screening. Therefore, bioassay-guided fraction and separation of the active component from these three broths were carried out which resulted in the isolation of seventeen compounds. Their structures were elucidated to be myxosporsidol A (1), trichodermin (2), myxosporsidol B (3), O-methyldihydrobotrydial (4), 2,5-di(hydroxymethyl)furan (5), trichophenol A (6), trichophenol B (7), trichophenol C (8), trichophenol D (9), coriloxin (10), zythiostromic acid A (11), radicicol (12), 3,5-dihydroxytoluene (13), 5-(hydroxymethyl)furfural (14), alveophomic acid (15), α-acetylorcinol (16) and curvulinic acid (17). Of these compounds identified, a sesquiterpene 1 and a acid 15 were novel compounds, and four phenolics 6–9 were novel chemical entities. Compound 2 exhibited significant growth inhibitory activities against A549, Ca9-22, TOV-21G-Tx and NCI/ADR-RES cell lines with GI50 values of 0.67, 0.48, 0.28 and 0.35 μM, respectively. Compound 12 exhibited significant growth inhibitory activities against A549, TOV-21G-Tx, HT-29 and SK-Hep-1 cell lines with GI50 values of 1.43, 0.68, 0.95 and 9.67 μM, respectively. Compounds 6–9 exhibited moderate growth inhibitory activities against A549 cell line with GI50 values of 25.61, 19.32, 16.19 and 24.31 μM, respectively. Compound 2 exhibited significant antimicrobial activities against Candida albicans, Cryptococcus neoformans and Saccharomyces cerevisiae with MIC values of 2, 1 and 1 μg/mL, respectively. Compound 12 exhibited moderate antimicrobial activities against these fungal strains with MIC values of 32, 16 and 32 μg/mL, respectively. In addition, 1 exhibited slight inhibitory activity on NO production of RAW264.7 cells induced by lipopolysaccharide with an IC50 value of 74.63 μM.
Description:	碩士指導教授-李宗徽委員-張芳榮委員-李慶國
Data Type:	thesis
Appears in Collections:	[Graduate Institute of Pharmacognosy Science] Dissertation/Thesis

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