真菌Alternaria sp.XZSBG-1的四氫蒽醌類次級(jí)代謝產(chǎn)物*

陳 彬，普布多吉，徐愛國，劉 嵐，朱 勛，林永成，蔣思萍

(1.西藏自治區(qū)高原生物研究所，西藏 拉薩850001;2. 中山大學(xué)化學(xué)與化學(xué)工程學(xué)院，廣東 廣州510275;3. 中山大學(xué)海洋科學(xué)學(xué)院, 廣東 廣州510275；4. 中山大學(xué)醫(yī)學(xué)院，廣東 廣州510275)

真菌Alternaria sp.XZSBG-1的四氫蒽醌類次級(jí)代謝產(chǎn)物*

陳 彬1,2，普布多吉1，徐愛國1，劉 嵐2,3，朱 勛4，林永成2，蔣思萍1

(1.西藏自治區(qū)高原生物研究所，西藏 拉薩850001;2. 中山大學(xué)化學(xué)與化學(xué)工程學(xué)院，廣東 廣州510275;3. 中山大學(xué)海洋科學(xué)學(xué)院, 廣東 廣州510275；4. 中山大學(xué)醫(yī)學(xué)院，廣東 廣州510275)

采用硅膠、C-18反相硅膠、Sephadex LH-20等柱色譜及高效液相色譜技術(shù)對(duì)真菌Alternariasp. XZSBG-1的次級(jí)代謝產(chǎn)物進(jìn)行系統(tǒng)研究；采用波譜分析及與文獻(xiàn)比對(duì)等方法鑒定化合物結(jié)構(gòu)；采用MTT法和比色法進(jìn)行抗腫瘤和酶抑制活性篩選。結(jié)果從真菌Alternariasp. XZSBG-1的發(fā)酵物中分離得到8個(gè)四氫蒽醌類化合物，分別鑒定為Alterporriol F’(1)、Alterporriol G’(2)、Alterporriol F(3)、Alterporriol G(4)、Altersolanol A(5)、Altersolanol F(6)、Tetrahydroaltersolanol B (7)和Tetrahydroaltersolanol D (8)；活性測試結(jié)果表明僅化合物6對(duì)結(jié)腸癌細(xì)胞株(HCT-116)和子宮癌細(xì)胞株(Hela)具有明顯抑制活性，IC50值分別為3.026和8.094 μmol/L。

Alternariasp.；次級(jí)代謝產(chǎn)物；四氫蒽醌；抗腫瘤活性

蒽醌，四氫蒽醌以及它們的衍生物作為次級(jí)代謝產(chǎn)物存在于許多植物、地衣及真菌中，并表現(xiàn)出良好的生物活性[1-5]。Alternaria是這兩類化合物的主要生物來源菌屬[6-12]。課題組研究人員在前期對(duì)鹽湖真菌Alternariasp. XZSBG-1的研究中，發(fā)現(xiàn)了系列二聚的蒽醌類次級(jí)代謝產(chǎn)物[13-14]。在此基礎(chǔ)上，我們又從中發(fā)現(xiàn)8個(gè)四氫蒽醌類化合物(圖1)，分別為Alterporriol F’ (1), Alterporriol G’ (2), Alterporriol F (3), Alterporriol G (4), Altersolanol A (5), Altersolanol F (6), Tetrahydroaltersolanol B (7) 和Tetrahydroaltersolanol D (8)；初步的活性研究發(fā)現(xiàn)，8個(gè)化合物對(duì)α-葡萄糖苷酶均無明顯抑制活性，僅有化合物Altersolanol F (6)對(duì)結(jié)腸癌細(xì)胞株(HCT-116)和子宮癌細(xì)胞株(Hela)具有明顯抑制活性，其IC50值分別為3.026和8.094 μmol/L。

1 實(shí)驗(yàn)試劑與儀器

UV-2501 PC紫外可見分光光度計(jì)(Shimadzu, Japan)，Bruker AVANCE 400型核磁共振譜儀(Bruker Biospin, Germany)，LCQ-DECA-XP型液相色譜-質(zhì)聯(lián)用儀(Thermo, USA)，Agilent 1260型高效液相色譜儀(HPLC)(Agilent, USA)。TLC硅膠(GF254)、柱層析硅膠(200～300目)均為青島海洋化工有限公司產(chǎn)品，Sephadex LH-20凝膠和C-18反相硅膠ODS-A均為北京綠百草科技有限公司產(chǎn)品；色譜純甲醇為Merck產(chǎn)品，其他試劑均為分析純，天津化學(xué)試劑廠產(chǎn)品。

2 實(shí)驗(yàn)方法

2.1 真菌分離

鹽湖沉積物樣品于2010年7月21日采自西藏自治區(qū)那曲地區(qū)班戈縣巴木措(E: 90°68′84.94″, N:31°32′96.46″, 海拔4 657 m)。將沉積物樣品中的腐殖部分經(jīng)稀釋涂布，得到10余株真菌。其中編號(hào)為XZSBG-1的菌株經(jīng)分子生物學(xué)鑒定為鏈格孢菌屬 (Alternariasp.)，命名為Alternariasp.XZSBG-1，GenBank 登錄號(hào)為HM622756；該菌種保存于西藏自治區(qū)高原生物研究所。

圖1 真菌Alternaria sp. XZSBG-1的四氫蒽醌類次級(jí)代謝產(chǎn)物Fig.1 Tetrahydroanthraquinone derivatives from Alternaria sp. XZSBG-1

2.2 發(fā)酵與提取

采用馬鈴薯葡萄糖液體培養(yǎng)基作為發(fā)酵培養(yǎng)基。將菌株種子培養(yǎng)液接種到盛有馬鈴薯葡萄糖液體培養(yǎng)基的1 L三角瓶中，共接種120瓶，常溫發(fā)酵培養(yǎng)28 d；加入少許乙酸乙酯終止發(fā)酵，并分批次進(jìn)行菌體和發(fā)酵液分離，發(fā)酵液用乙酸乙酯等體積萃取3次，菌體陰干后用甲醇浸提3次，濃縮乙酸乙酯萃取液和甲醇浸提液，合并，共得浸膏112 g。

2.3 分離純化

將浸膏用的乙酸乙酯和甲醇充分溶解，過濾，濾液用1 000 mL 200目硅膠拌樣，干燥后濕法上柱，進(jìn)行柱層析分離。使用石油醚-乙酸乙酯體系(V(乙酸乙酯)∶V(石油醚)梯度分別為1∶100,1∶20, 1∶10, 1∶5, 1∶3, 1∶1, 2∶1，4∶1, 1∶0)和乙酸乙酯-甲醇體系(V(甲醇)∶V(乙酸乙酯)梯度分別為1∶50, 1∶20, 1∶10, 1∶5, 1∶0)分別對(duì)柱子進(jìn)行梯度洗脫，得到組分Fr.1-Fr.14。將組分Fr.5再進(jìn)行柱層析，洗脫體系為甲醇-氯仿(V(甲醇)∶V(氯仿)梯度為1∶100， 1∶90，1∶80，1∶70， 1∶60， 1∶50， 1∶40， 1∶30， 1∶20， 1∶10， 1∶9， 1∶8， 1∶7， 1∶6， 1∶5， 1∶4)，分別得到化合物6(6.0 mg),7(5.6 mg),8(3.8 mg)。采用甲醇-氯仿體系(V(甲醇)∶V(氯仿)梯度為1∶100， 1∶90， 1∶80，1∶70， 1∶60， 1∶50， 1∶40，1∶30， 1∶20， 1∶10， 1∶9， 1∶8， 1∶7， 1∶6， 1∶5， 1∶4)對(duì)Fr.6進(jìn)行柱層析洗脫，分別得到化合物5 (5.6 mg)，和Fr.6-1和Fr.6-2。采用HPLC，選擇甲醇-水作為流動(dòng)相，從Fr.6-1分離得到化合物1和2的混合物(11.6 mg)，從Fr.6-2得到化合物3 (4.3 mg)和4 (3.5 mg)。

2.4 活性測試

2.4.1 α-葡萄糖苷酶抑制活性的測試 采用比色法測定化合物對(duì)α-葡萄糖苷酶的抑制活性[15]。結(jié)果顯示8個(gè)化合物對(duì)α-葡萄糖苷酶均沒有明顯的抑制活性。

2.4.2 抗腫瘤細(xì)胞株的活性測試 采用MTT法測定化合物對(duì)人乳腺癌細(xì)胞株MCF-7/ADR、MDA-MB-435、人肝癌細(xì)胞株Hep3B、HepG2、人前列腺癌細(xì)胞株P(guān)C-3、人結(jié)腸癌細(xì)胞株HCT-116和子宮癌細(xì)胞株Hela等7株細(xì)胞的抑制活性[16]?；衔?、7、8沒有進(jìn)行抗腫瘤細(xì)胞株活性測試實(shí)驗(yàn)。結(jié)果表明在這6個(gè)化合物中，化合物1和2對(duì)Hep3B、MDA-MB-435以及PC-3有抑制活性，在50 μmol/L濃度下，抑制率分別達(dá)到71.8%、88.7%和93.4%；化合物3和4僅對(duì)MDA-MB-435具有輕微的抑制活性，抑制率為48.3%；化合物6則對(duì)結(jié)腸癌細(xì)胞株(HCT-116)和子宮癌細(xì)胞株(Hela)具有明顯抑制活性，IC50值分別為3.026和8.094 μmol/L。

2.5 化合物波譜數(shù)據(jù)

化合物1：橙紅色無定型粉末，θmp>300 ℃，易溶于甲醇；ESI-MSm/z：601 [M-H]-,分子式為C32H26O12。1H NMR (400 MHz, DMSO)δ: 2.32 (m, 1H, H-1a), 2.79 (m, 1H, H-1b), 3.67 (d, 1H, 8.0 Hz, H-2), 4.03 (d, 1H, 7.2 Hz, H-4), 6.90 (s, 1H, H-7), 3.683(s, 3H, H-11), 1.16 (s, 3H, H-12), 4.59 (d, 1H, 6.8 Hz, OH-2), 4.25 (s, 1H, OH-3), 5.42 (d, 1H, 7.60 Hz,OH-4), 13.11 (s, 1H, OH-8), 7.56 (s, 1H, H-1’), 7.69 (d, 1H, 0.8 Hz, H-4’), 6.93 (s, 1H, H-7’), 3.681 (s, 3H, H-11’), 2.19 (s, 3H, H-12’), 10.02 (br, 1H, OH-2’), 13.61(br, 1H, OH-8’);13C NMR (100 MHz, DMSO)δ: 28.8 (C-1), 66.7 (C-2), 71.9 (C-3), 69.0 (C-4), 142.6 (C-4a), 123.2 (C-5), 164.4 (C-6), 103.6 (C-7), 163.8 (C-8), 108.9 (C-8a), 188.4 (C-9), 143.7 (C-9a), 183.3 (C-10), 131.1 (C-10a), 56.7 (C-11), 21.8 (C-12), 110.5 (C-1’), 161.3 (C-2’), 125.2 (C-3’), 130.2 (C-4’), 132.2 (C-4a’), 122.3 (C-5’), 165.0 (C-6’), 104.0 (C-7’), 164.9 (C-8’), 110.0 (C-8a’), 186.7 (C-9’), 132.4 (C-9a’), 181.1 (C-10’), 128.9 (C-10a), 56.7 (C-11’), 16.1 (C-12’)；以上數(shù)據(jù)與文獻(xiàn)[8,10]報(bào)道對(duì)照基本一致，故鑒定化合物1為Alterporriol F’。

化合物2：橙紅色無定型粉末，θmp>300 ℃，易溶于甲醇；ESI-MSm/z：601 [M-H]-, 分子式為C32H26O12。1H NMR (400 MHz, DMSO)δ: 2.32 (m, 1H, H-1a), 2.788 (m, 1H, H-1b), 3.67 (d, 1H, 8.0 Hz, H-2), 4.05 (d, 1H, 7.6 Hz, H-4), 6.90 (s, 1H, H-7), 3.713(s, 3H, H-11), 1.16 (s, 3H, H-12), 4.62 (d, 1H, 6.8 Hz, OH-2), 4.32 (s, 1H, OH-3), 5.30 (d, 1H, 7.20 Hz, OH-4), 13.14 (s, 1H, OH-8), 7.56 (s, 1H, H-1’), 7.67 (d, 1H, 0.8 Hz, H-4’), 6.94 (s, 1H, H-7’), 3.711 (s, 3H, H-11’), 2.19 (s, 3H, H-12’), 10.02 (br, 1H, OH-2’), 13.66(br, 1H, OH-8’);13C NMR (100 MHz, DMSO)δ: 28.7 (C-1), 66.6 (C-2), 72.0 (C-3), 68.9 (C-4), 142.7 (C-4a), 123.3 (C-5), 164.4 (C-6), 103.6 (C-7), 163.9 (C-8), 108.9 (C-8a), 189.0 (C-9), 143.6 (C-9a), 183.1 (C-10), 130.5 (C-10a), 56.8 (C-11), 21.8 (C-12), 110.4 (C-1’), 161.2 (C-2’), 125.2 (C-3’), 130.2 (C-4’), 132.2 (C-4a’), 122.8 (C-5’), 165.2 (C-6’), 104.0 (C-7’), 165.1 (C-8’), 109.9 (C-8a’), 186.6 (C-9’), 132.4 (C-9a’), 180.9 (C-10’), 128.9 (C-10a), 56.8 (C-11’), 16.1 (C-12’)；以上數(shù)據(jù)與文獻(xiàn)[8,10]報(bào)道基本一致，故鑒定2為Alterporriol G’。

化合物3：橘紅色無定型粉末，易溶于甲醇；ESI-MSm/z：653 [M-H]-；分子式為C32H30O15;1H NMR (400 MHz, DMSO) δ: 3.55 (m, 1H, H-1), 3.69 (m, 1H, H-2), 4.08 (m, 1H, H-3), 6.93 (s, 1H, H-7), 3.69 (s, 3H, H-11), 1.17 (s, 3H, H-12), 2.30 (m, 1H, H-1a’), 2.80 (m, 1H, H-1b’), 4.47 (m, 1H, H-2’), 3.42 (m, 1H, H-4’), 6.91(s, 1H, H-7’), 3.69 (s, 3H, H-11’), 1.15(s, 3H, H-12’);13C NMR (100 MHz, DMSO)δ: 73.8 (C-1), 66.7 (C-2), 69.0 (C-3), 68.5 (C-4), 143.8 (C-4a), 109.3 (C-5), 164.6 (C-6), 103.9 (C-7), 164.0 (C-8), 122.6 (C-8a), 188.8 (C-9), 142.8 (C-9a), 183.8 (C-10), 129.1 (C-10a), 56.9 (C-11), 21.9 (C-12), 28.8 (C-1’), 68.4 (C-2’), 72.0 (C-3’), 73.0 (C-4’), 143.5 (C-4a’), 108.9 (C-5’), 164.9 (C-6’), 103.6 (C-7’), 164.2 (C-8’), 122.6 (C-8a’), 188.4 (C-9’), 142.8 (C-9a’), 183.2 (C-10’), 129.0 (C-10a), 56.9 (C-11’), 22.3 (C-12’)；以上數(shù)據(jù)與文獻(xiàn)[17]報(bào)道對(duì)照基本一致，故鑒定化合物3為Alterporriol F。

化合物4：橘紅色無定型粉末，易溶于氯仿；ESI-MSm/z：653 [M-H]-； 分子式為C32H30O15;1H NMR (400 MHz, DMSO)δ: 3.55 (m, 1H, H-1), 3.69 (m, 1H, H-2), 4.06 (m, 1H, H-3),6.91 (s, 1H, H-7), 3.69 (s, 3H, H-11), 1.15 (s, 3H, H-12), 2.31 (m, 1H, H-1a’), 2.82 (m, 1H, H-1b’), 4.45 (m, 1H, H-2’), 3.42 (m, 1H, H-4’), 6.89 (s, 1H, H-7’), 3.69 (s, 3H, H-11’), 1.15(s, 3H, H-12’);13C NMR (100 MHz, DMSO)δ: 73.9 (C-1), 66.8 (C-2), 69.0 (C-3), 68.4 (C-4), 143.8 (C-4a), 109.4 (C-5), 163.9 (C-6), 104.2 (C-7), 163.6 (C-8), 122.0 (C-8a), 188.8 (C-9), 142.9 (C-9a), 184.2 (C-10), 130.0 (C-10a), 56.8 (C-11), 21.9 (C-12), 28.9 (C-1’), 68.3 (C-2’), 72.0 (C-3’), 73.0 (C-4’), 143.5 (C-4a’), 109.0 (C-5’), 163.9 (C-6’), 104.0 (C-7’), 163.8 (C-8’), 121.8 (C-8a’), 188.5 (C-9’), 142.7 (C-9a’), 183.2 (C-10’), 129.6 (C-10a), 56.8 (C-11’), 22.3 (C-12’)；以上數(shù)據(jù)與文獻(xiàn)[17]報(bào)道對(duì)照基本一致，故鑒定化合物4為Alterporriol G。

化合物5：橙色無定型粉末，易溶于甲醇；ESI-MSm/z：335 [M-H]-； 分子式為C16H16O8;1H NMR (400 MHz, DMSO)δ: 4.49 (dd, 1H, 6.89, 6.06 Hz, H-1), 3.64 (dd, 1H, 6.06, 6.89 Hz, H-2), 4.32 (d, 1H, 5.10 Hz, H-4), 7.03 (d, 1H, 2.5 Hz, H-5), 6.84 (d, 1H, 2.5 Hz, H-7), 3.91 (s, 3H, H-11), 1.24 (s, 3H, H-12), 5.04 (d, 1H, 5.18 Hz, OH-1), 4.87 (d, 1H, 6.41 Hz, OH-2), 4.45 (d, 1H, 5.10 Hz, OH-3), 5.67 (d, 1H, 6.08 Hz, OH-4), 12.16(br, 1H, OH-8);13C NMR (100 MHz, DMSO)δ: 68.8 (C-1), 74.1 (C-2), 73.2 (C-3), 68.7 (C-4), 142.3 (C-4a), 106.9 (C-5), 165.8 (C-6), 106.2 (C-7), 163.4 (C-8), 109.8 (C-8a), 183.9 (C-9), 144.7 (C-9a), 188.7 (C-10), 133.6 (C-10a), 56.5 (C-11), 22.5 (C-12); 以上數(shù)據(jù)與文獻(xiàn)[8]報(bào)道對(duì)照基本一致，故鑒定化合物5為Altersolanol A。

化合物6：黃色針狀晶體，易溶于甲醇；ESI-MSm/z：319 [M-H]-；分子式為C16H16O7;1H NMR (400 MHz, DMSO)δ: 2.35 (dd, 1H, 9.7, 19.4 Hz, H-1a), 2.89 (dd, 1H, 5.90, 19.4 Hz H-1b), 3.76 (d, 1H, 9.5 Hz, H-2), 4.34 (d, 1H, 6.0 Hz, H-4), 7.04 (d, 1H, 2.5 Hz, H-5), 6.82 (d, 1H, 2.5 Hz, H-7), 3.90 (s, 3H, H-11), 1.28 (s, 3H, H-12);13C NMR (100 MHz, DMSO)δ: 29.5 (C-1), 67.2 (C-2), 72.4 (C-3), 69.7 (C-4), 144.4 (C-4a), 107.4 (C-5), 166.1 (C-6), 106.1 (C-7), 163.8 (C-8), 130.6 (C-8a), 188.6 (C-9), 143.5 (C-9a), 183.4 (C-10), 133.9 (C-10a), 56.8 (C-11), 22.3 (C-12); 以上數(shù)據(jù)與文獻(xiàn)[18]報(bào)道對(duì)照基本一致，故鑒定6為Altersolanol F。

化合物7：黃色油狀，易溶于甲醇；ESI-MSm/z：303 [M-H]-； 分子式C16H16O6;1H NMR (400 MHz, DMSO)δ: 2.22 (m, 1H, H-1a), 2.40 (m, 1H, H-1b), 3.54 (m, 1H, H-2), 2.50 (m, 1H, H-4a), 2.70 (m, 1H, H-4b), 7.00 (d, 1H, 2.1 Hz, H-5), 6.78 (d, 1H, 2.1 Hz, H-7), 3.88 (s, 3H, H-11), 1.16 (s, 3H, H-12), 12.24 (br, 1H, OH-8);13C NMR (100 MHz, DMSO)δ: 35.8 (C-1), 70.2 (C-2), 69.0 (C-3), 29.4 (C-4), 142.3 (C-4a), 105.6 (C-5), 165.4 (C-6), 106.9 (C-7), 163.8 (C-8), 108.9 (C-8a), 183.1 (C-9), 142.7 (C-9a), 187.8 (C-10), 133.3 (C-10a), 56.3 (C-11), 25.2 (C-12); 以上數(shù)據(jù)與文獻(xiàn)[8]報(bào)道對(duì)照基本一致，故鑒定7為Tetrahydroaltersolanol B。

化合物8：無色針狀晶體，溶于丙酮和甲醇；ESI-MSm/z：307 [M-H]-；C16H20O6；1H NMR (400 MHz, acetone-d6)δ：6.37 (d, 1H, 2.45 Hz, H-6), 6.73 (dd, 1H, 2.45,1.21 Hz, H-8), 4.28 (dd, 1H, 7.64, 5.68 Hz, H-9), 3.79 (dd, 1H, 6.80 Hz, 10.21 Hz, H-3), 2.38 (dd, 3H, 3.76, 6.12 Hz, H-4a), 1.97 (ddd, 1H, 12.0, 5.98, 3.68 Hz, H-9a), 3.82 (s, 3H, OCH3-11), 1.23 (d, 1H, 12.0 Hz, H-1a); 2.19 (dd, 1H, 3.72, 6.84 Hz, H-1b); 1.46 (dd, 1H, 12.4, 12.0 Hz, H-4a); 2.12 (ddd, 1H, 4.0, 4.0, 6.76 Hz, H-4b); 1.16 (s, 3H, H-12); 12.89(s, 1H, OH-5); 5.61(d, 1H, 7.52 Hz, OH-9); 4.42(d, 1H, 6.40 Hz, OH-3); 3.76(s, 1H, OH-2);13C NMR (100 MHz，aceton-d6)δ：42.0 (C-1), 69.5(C-2), 73.5(C-3), 29.3(C-4), 47.0(C-4a), 164.5(C-5), 99.1 (C-6), 165.9 (C-7), 104.0(C-8), 151.60 (C-8a), 70.7(C-9), 41.2(C-9a), 202.9 (C-10), 109.2 (C-10a), 55.7(C-11), 27.1 (C-12)。以上數(shù)據(jù)與文獻(xiàn)[10]報(bào)道對(duì)照基本一致，故鑒定化合物8為Tetrahydroaltersolanol D。

3 結(jié)果與討論

化合物1和2、3和4，均是由單體化合物通過C-5-C-5’鍵合形成的二聚物，而C-6和C-10a與C-6’和C-10a’關(guān)于鍵軸C-5-C-5’具有不對(duì)稱性，因而形成軸手性，而四氫蒽醌類化合物二聚體的CD光譜的曲線趨勢主要由化合物的軸手性貢獻(xiàn)的[16]。通過比對(duì)文獻(xiàn)[17-18]，對(duì)比CD光譜譜圖，推斷出化合物1和3均為軸手性aR型，化合物2和4均為軸手性aS。

蒽醌類化合物普遍有多種生物活性，如抗腫瘤、抗菌消炎、舒張心血管等作用[19]，還有些蒽醌類化合物對(duì)中樞神經(jīng)系統(tǒng)有作用，如金絲桃素，被國內(nèi)外認(rèn)為是具有抗老年癡呆、促智、抗抑郁等方面的中樞神經(jīng)系統(tǒng)的藥物[20-21]。本文對(duì)8個(gè)蒽醌類化合物進(jìn)行了抗人乳腺癌細(xì)胞株MCF-7/ADR、MDA-MB-435、人肝癌細(xì)胞株Hep3B、HepG2、人前列腺癌細(xì)胞株P(guān)C-3、人結(jié)腸癌細(xì)胞株HCT-116和子宮癌細(xì)胞株Hela等方面活性的篩選，并進(jìn)行了α-葡萄糖苷酶的抑制活性試驗(yàn)，實(shí)驗(yàn)發(fā)現(xiàn)多數(shù)化合物沒有明顯的抗腫瘤活性，也沒有明顯抑制α-葡萄糖苷酶的活性。依據(jù)化合物的抗腫瘤細(xì)胞株活性實(shí)驗(yàn)結(jié)果，結(jié)合化合物的結(jié)構(gòu)，可以發(fā)現(xiàn)具有環(huán)己烯結(jié)構(gòu)的四氫蒽醌是活性官能團(tuán)，當(dāng)環(huán)己烯結(jié)構(gòu)中尚有亞甲基未被羥基或甲基取代時(shí)，化合物具有活性，可以推斷出亞甲基是該類型化合物的活性位點(diǎn)，這種情況在黃才歡等[9]的研究中也發(fā)現(xiàn)過。由于沒有測試化合物7的抗腫瘤細(xì)胞株活性，因此需要進(jìn)一步通過實(shí)驗(yàn)驗(yàn)證。

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Tetrahydroanthraquinone derivatives fromAlternariasp. XZSBG-1

CHENBin1,2,PUBUDuoji1,XUAiguo1,LIULan2,3,ZHUXun4,LINYongcheng2,JIANGSiping1

(1. Tibet Platesu Institute of Biology, Lhasa 850001, China;2. School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 China;3. School of Marine Sciences, Sun Yat-sen University, Guangzhou 510275, China;4. Zhongshan School of Medicine, SunYat-sen University, Guangzhou 510275, China)

To study the secondary metabolites ofAlternariasp. XZSBG-1 from Tibet. The chemical compounds were isolated and purified by silica gel, Sephadex LH-20, ODS-18 column chromatography, and HPLC. Their structures were characterized by NMR and MS analyses. The antitumor and enzyme inhibitory activities were investigated using MTT and colourimetry methods, respectively. Eight tetrahydroanthraquinone derivatives were isolated from the extract of the fungal strainAlternariasp. XZSBG-1, and their structures were determined to be Alterporriol F’ (1),Alterporriol G’ (2), Alterporriol F (3), Alterporriol G (4), Altersolanol A (5), Altersolanol F (6), Tetrahydroaltersolanol B (7) and Tetrahydroaltersolanol D (8). Only the compound 6 showed obvious inhibitory activity against HCT-116 and HeLa cell lines with the IC50values 3.026 and 8.094 μmol/L, respectively.

Alternariasp.; secondary metabolites; tetrahydroanthraquinones; antitumor activity

10.13471/j.cnki.acta.snus.2016.01.016

2015-07-03

西藏自治區(qū)科技計(jì)劃重點(diǎn)資助項(xiàng)目 (毛瓣綠絨蒿等瀕危藏藥材次級(jí)代謝及其與宿主互惠共存關(guān)系的研究,2011)

陳彬(1977年生)，男;研究方向：天然產(chǎn)物化學(xué)，特殊真菌次級(jí)代謝;通訊作者：蔣思萍，林永成;E-mail:tpibjiangsp@126.com， ceslyc@mail.sysu.edu.cn

O629.9

A

0529-6579(2016)01-0091-05