波罗蜜(Artocarpus heterophyllus Lam.)为桑科波罗蜜属植物, 以其硕大的果实而著称, 又名“树婆罗”、“牛肚子果”、“蜜冬瓜”等, 主要分布于亚洲的热带及亚热带地区, 在我国东南和华南的福建、台湾、广东、广西及海南等省多有栽培。《本草纲目》载, 波罗蜜“甘微酸, 平, 无毒”, 具有“止渴解烦, 醒酒, 益气”的功效[1]。波罗蜜的幼果、树汁、叶、树皮在当地民间入药, 用于消肿解毒、跌打损伤、肺热咳嗽、产妇无乳汁、食欲不振、饮酒过度等[2]。国内外对波罗蜜的化学成分研究表明, 其主要含有黄酮[3]、二苯乙烯[4]、2-芳基苯并呋喃[5]等酚性成分, 具有细胞毒[6]、抗炎[7]、抗氧化[8]、抗中性粒细胞呼吸爆发[9]以及抑制酪氨酸酶[10]的活性。组织蛋白酶K (cathepsin K, CatK)是治疗骨质疏松症的一个新型靶点, 近年来证明其抑制剂对骨质疏松症有明显的治疗效果[11, 12]。本课题组前期发现波罗蜜的乙醇提取物对组织蛋白酶K具有一定的抑制效果, 并从中分离一些活性单体[13, 14]。作为该工作的延续, 本课题组继续对波罗蜜的乙醇提取物进行分离, 获得了10个异戊烯基取代的黄酮类化合物(图 1), 分别鉴定为artoheteroid E (1)、cycloheterophyllin (2)、artelasto xanthone (3)、artoindonesianin Q (4)、柘树黄酮C (5)、8-(γ, γ-dimethylallyl)-5, 2', 4'-trihydroxy-7-methoxyflavone (6)、桑皮酮T (7)、6-(3-methylbut-2-enyl) apigenin (8)、5, 7, 2', 4'-四羟基-6-异戊烯基黄酮(9)和albanin A (10)。其中, 化合物1为新化合物, 化合物2~4为首次从该植物中分离得到。所有分离的化合物进行了抑制CatK活性筛选, 其中, 化合物3~5、7和10对CatK具有不同程度的抑制作用, 其IC50值分别为0.9、1.6、4.5、24.5、63.5 µmol·L-1。
化合物1为黄色无定形粉末(丙酮)。HR-ESI-MS给出准分子离子峰m/z 449.161 1 [M-H]- (计算值为449.160 6), 确定其分子式为C26H26O7。红外光谱(IR)显示其结构中存在羟基(3 447 cm-1)、甲基(2 927 cm-1)、羰基(1 654 cm-1)、苯环(1 610 cm-1)等特征信号峰。紫外光谱(UV)显示在262、315及371 nm处有特征性吸收。1H NMR谱(表 1)显示了一个与羰基螯合的羟基δH 13.20 (1H, s, HO-5); 2个间位耦合芳香质子信号δH 6.27 (1H, br s, H-6)和6.69 (1H, br s, H-8);一组典型的γ, γ二甲基烯丙基侧链取代基的质子信号δH 3.33 (2H, d, J = 7.1 Hz, H-16)、5.19 (1H, t, J = 7.1 Hz, H-17)、1.76 (3H, s, H-19)和1.67 (3H, s, H-20)[15, 16]; 一个ABX自旋耦合体系δH 2.35 (1H, t, J = 15.4 Hz, Ha-11)、3.19 (1H, dd, J = 15.2, 7.1 Hz, Hb-11)和3.38 (1H, dd, J = 15.5, 7.1 Hz, H-12);两个甲基δH 1.35 (3H, s, H-14)和1.64 (3H, s, H-15);一个甲氧基δH 4.01 (3H, s, MeO-4')。化合物1的1H NMR谱数据与已知化合物artoheteroid C (图 1)[13]非常相似。两者氢谱差异主要体现在:化合物1的H-3'信号消失, 而多出了一组归属于γ, γ-二甲基烯丙基的质子信号。这提示, 化合物1的C-3'位发生了一个γ, γ-二甲基烯丙基型的侧链取代。分析1的13C NMR数据(表 1)并利用HMQC谱对其碳信号进行归属, 支持了这个推测:与artoheteroid C相比, 化合物1多出了5个碳信号δC 23.7 (C-16)、123.8 (C-17)、131.4 (C-18)、17.9 (C-19)和25.9 (C-20), 这是γ, γ-二甲基烯丙基型异戊二烯取代基的典型碳信号。化合物1的HMBC谱(图 2)显示, H-16与C-2'、C-3'、C-4'的相关, H-17与C-3'的相关。这进一步证实了γ, γ-二甲基烯丙基侧链取代位于C-3'。甲氧基质子信号δH 4.01与C-3'的HMBC相关证明了甲氧基取代在C-4'位。化合物1具有旋光活性, 比旋光值{[α]D25-3.5 (c 0.1, MeOH)}与来自同种植物的artoheteroid C的比旋光值{[α]D25-2.4 (c 0.3, MeOH)}[13]相近, 提示他们的C-12具有相同的立体构型R。因此, 化合物1鉴定为图 1所示的结构, 它是一个新的异戊烯基黄酮, 命名为artoheteroid E。
对所有分离的化合物进行了组织蛋白酶K活性评价。如表 2所示, 化合物3~5、7和10显示不同程度的抑制作用。观察这些活性化合物的结构可发现初步的构效规律: B环上C-2'/C-5' (3和4)或C-2'/C-4' (5, 7, 10)的二游离酚羟基取代及C环C-3位置的异戊烯基取代对于活性是必须的; B环2', 5'-二羟基取代型化合物(3和4)的活性强于2', 4'-二羟基取代型化合物(5、7、10)。
Bruker AX-600型核磁共振波谱仪(瑞士Bruker公司); Finnigan TSQ 700型质谱仪(美国Finnigan公司); UV-1800紫外可见分光光度计和IRAffinity-1傅立叶变换红外光谱仪(日本岛津公司); Agilent 1260分析型高效液相色谱仪(美国安捷伦科技有限公司); LC-3000高效液相色谱仪(北京创新通恒科技有限公司); Sephadex LH-20 (瑞士Pharmacia公司); YMC-pack ODS半制备柱(250 mm × 10 mm, 5 μm) (日本YMC公司); MCI CHP-20P树脂、HP-20大孔树脂(日本三菱化学公司)。薄层色谱硅胶板(烟台江友硅胶开发有限公司); 色谱纯甲醇、乙腈(美国天地有限公司); N-[N-(L-3-trans-carboxirane-2-carbonyl)-L-leucyl]-agmatine (E64, 上海阿拉丁科技股份有限公司); N-CBZ-PHE-ARG7-AMEDO-4-METHYLCOUMARI (美国R & D Systems); CatK (美国Enzo Life sciences)。其他所用试剂均为分析纯(西陇化工股份有限公司)。
波罗蜜根于2013年3月采自广西壮族自治区南宁市, 由江西中医药大学中药资源与民族药研究中心慕泽泾讲师鉴定为桑科波罗蜜属波罗蜜 Artocarpus heterophyllus Lam.的根, 凭证标本(TCM01-01-2013)保存于江西中医药大学中药资源与民族药研究中心标本室。
1 提取与分离取干燥波罗蜜根部17.0 kg, 粉碎后过筛, 室温下用95%乙醇浸提3次(药材与溶剂1:10), 得到浸出液, 过滤后合并, 减压浓缩得总浸膏1.5 kg。将总浸膏与水1:1混悬, 依次用石油醚、氯仿、醋酸乙酯、正丁醇萃取, 得到石油醚部位213.3 g、氯仿部位574.0 g、醋酸乙酯部位382.0 g、正丁醇部位152.4 g。氯仿部位经大孔树脂柱色谱, 用乙醇-水(0:100 → 100:0)梯度洗脱得组分Fr.1~11。Fr.7经MCI CHP-20P树脂柱色谱, 用乙醇-水(50:100 → 100:0)梯度洗脱, 并结合Sephadex LH-20柱色谱和半制备高效液相色谱得到化合物1 (3.0 mg, 40%乙腈, tR 25 min)、2 (10 mg, 80%乙腈, tR 25 min)、3 (10 mg, 50%乙腈tR 30 min)、4 (6 mg, 50%乙腈, tR 38 min)、5 (2 mg, 60%乙腈, tR 40 min)、6 (8 mg, 50%乙腈, tR 27 min)、7 (33 mg, 55%乙腈, tR 50 min)、8 (2.8 mg, 50%乙腈, tR 50 min)、9 (11 mg, 40%乙腈, tR 58 min)和10 (6 mg, 40%乙腈, tR 33 min)。
2 结构鉴定化合物1 黄色无定形粉末(丙酮), 10%浓硫酸-乙醇溶液喷雾后加热显黄色。[α]D25-3.5 (c 0.1, MeOH); HR-ESI-MS m/z 449.161 1 [M-H]- (计算值为449.160 6), 确定分子式为C26H26O7。不饱和度为14。UV吸收峰λmax (log ε): 262 (4.2)、315 (3.9)、371 (4.0) nm。红外光谱显示结构中存在羟基(3 447 cm-1)、甲基(2 927 cm-1)、羰基(1 654 cm-1)、苯环(1 610 cm-1)等特征信号峰。NMR数据见表 1。
化合物2 黄色无定形粉末(甲醇), 10%浓硫酸-乙醇溶液喷雾后加热显黄色。ESI-MS m/z 501.19 [M-H]-; 1H NMR (CD3OD, 600 MHz) δH 7.18 (1H, s, H-6'), 6.65 (1H, d, J = 10.0 Hz, H-16), 6.35 (1H, s, H-3'), 6.10 (1H, d, J = 9.4 Hz, H-11), 5.66 (1H, d, J = 10.0 Hz, H-17), 5.45 (1H, d, J = 9.4 Hz, H-12), 5.24 (1H, t, J = 6.8 Hz, H-22), 3.52 (1H, dd, J =14.4, 7.2 Hz, Hb-21), 3.46 (1H, dd, J = 14.4, 7.1 Hz, Ha-21), 1.95 (3H, s, H-15), 1.87 (3H, s, H-24), 1.71 (6H, s, H-14, 25), 1.45 (3H, s, H-19), 1.44 (3H, s, H-20); 13C NMR (CD3OD, 150 MHz) δC 157.6 (C-2), 110.0 (C-3), 179.9 (C-4), 154.8 (C-5), 106.4 (C-6), 157.5 (C-7), 109.0 (C-8), 155.4 (C-9), 105.5 (C-10), 107.9 (C-1'), 153.2 (C-2'), 106.1 (C-3'), 152.6 (C-4'), 142.0 (C-5'), 110.4 (C-6'), 70.3 (C-11), 122.4 (C-12), 139.6 (C-13), 25.9 (C-14), 18.7 (C-15), 116.6 (C-16), 129.2 (C-17), 79.0 (C-18), 28.4 (C-19), 28.5 (C-20), 22.3 (C-21), 123.3 (C-22), 132.7 (C-23), 26.0 (C-24), 18.4 (C-25)。以上数据均与文献[17, 18]对照后基本一致, 故鉴定为cycloheterophyllin。
化合物3 黄色无定形粉末(甲醇), 10%浓硫酸-乙醇溶液喷雾后加热显黄色。ESI-MS m/z 433.13 [M-H]-; 1H NMR (CD3OD, 600 MHz) δH 6.76 (1H, d, J = 10.0 Hz, H-16), 6.43 (1H, d, J = 2.0 Hz, H-8), 6.19 (1H, d, J = 2.0 Hz, H-6), 5.69 (1H, d, J = 10.0 Hz, H-17), 4.66 (1H, s, Hα-14), 4.25 (1H, s, Hβ-14), 3.95 (1H, d, J = 6.3 Hz, H-12), 3.35 (1H, dd, J = 6.7, 15.8 Hz, Hα-11), 2.44 (1H, dd, J = 6.7, 15.8 Hz, Hβ-11), 1.78 (3H, s, H-15), 1.49 (3H, s, H-20), 1.47 (3H, s, H-19); 13C NMR (CD3OD, 150 MHz) δC 162.1 (C-2), 112.2 (C-3), 181.6 (C-4), 163.0 (C-5), 100.0 (C-6), 165.4 (C-7), 95.0 (C-8), 158.1 (C-9), 105.0 (C-10), 108.2 (C-1'), 146.3 (C-2'), 111.5 (C-3'), 145.8 (C-4'), 137.6 (C-5'), 129.7 (C-6'), 22.6 (C-11), 38.4 (C-12), 145.6 (C-13), 112.0 (C-14), 21.9 (C-15), 117.7 (C-16), 129.9 (C-17), 78.5 (C-18), 28.1 (C-19), 28.1 (C-20)。以上数据与文献[19]对照后基本一致, 故鉴定为artelastoxanthone。
化合物4 黄色无定形粉末(甲醇), 10%浓硫酸-乙醇溶液喷雾后加热显黄色。ESI-MS m/z 397.13 [M-H]-; 1H NMR (CD3OD, 600 MHz) δH 6.73 (1H, s, H-6'), 6.60 (1H, s, H-3'), 6.43 (1H, d, J = 2.2 Hz, H-8), 6.30 (1H, d, J = 2.2 Hz, H-6), 5.08 (1H, t, J = 7.0 Hz, H-12), 3.84 (3H, s, MeO-7), 3.72 (3H, s, MeO-4'), 3.03 (2H, d, J = 6.7 Hz, H-11), 1.59 (3H, s, H-15), 1.38 (3H, s, H-14); 13C NMR (CD3OD, 150 MHz) δC 163.0 (C-2), 122.2 (C-3), 183.6 (C-4), 163.3 (C-5), 99.0 (C-6), 167.0 (C-7), 92.8 (C-8), 159.6 (C-9), 105.9 (C-10), 113.5 (C-1'), 149.8 (C-2'), 101.3 (C-3'), 152.5 (C-4'), 139.9 (C-5'), 117.8 (C-6'), 24.9 (C-11), 122.6 (C-12), 132.8 (C-13), 25.9 (C-14), 17.6 (C-15), 56.6 (MeO-7), 56.3 (MeO-4')。以上与文献[20]报道artoindonesianin Q的数据基本一致, 故鉴定为artoindonesianin Q。
化合物5 浅黄色无定形粉末(甲醇), 10%浓硫酸-乙醇溶液喷雾后加热显黄色。ESI-MS m/z421.16 [M-H]-; 1H NMR (CD3OD, 600 MHz) δH 7.05 (1H, d, J = 8.3 Hz, H-6'), 6.40 (1H, d, J = 2.2 Hz, H-3'), 6.39 (1H, dd, J = 8.3, 2.2 Hz, H-5'), 6.30 (1H, s, H-8), 5.25 (1H, t, J = 7.2 Hz, H-17), 5.08 (1H, t, J = 7.0 Hz, H-12), 3.32 (2H, overlap, H-16), 3.08 (2H, d, J = 7.0 Hz, H-11), 1.78 (3H, s, H-20), 1.67 (3H, s, H-19), 1.58 (3H, s, H-15), 1.38 (3H, s, H-14); 13C NMR (CD3OD, 150 MHz) δC 163.2 (C-2), 121.7 (C-3), 183.6 (C-4), 159.9 (C-5), 112.4 (C-6), 163.3 (C-7), 93.6 (C-8), 157.7 (C-9), 105.2 (C-10), 113.5 (C-1'), 157.8 (C-2'), 103.7 (C-3'), 161.8 (C-4'), 107.9 (C-5'), 132.6 (C-6'), 24.9 (C-11), 122.9 (C-12), 132 (C-13), 25.9 (C-14), 17.9 (C-15), 22.3 (C-16), 123.6 (C-17), 131.9 (C-18), 26.0 (C-19), 17.6 (C-20)。以上数据与文献[21]对照后基本一致, 故鉴定为柘树黄酮C。
化合物6 黄色无定形粉末(DMSO), 10%浓硫酸-乙醇溶液喷雾后加热显黄色。ESI-MS m/z 367.12 [M-H]-; 1H NMR (DMSO-d6, 600 MHz) δH 7.87 (1H, d, J = 8.8 Hz, H-6'), 7.15 (1H, s, H-6), 6.66 (1H, overlap, H-3'), 6.65 (1H, s, H-3), 6.57 (1H, dd, J = 2.3, 8.8 Hz, H-5'), 5.27 (1H, m, H-12), 4.03 (3H, s, MeO-7), 3.58 (2H, d, J = 6.8 Hz, H-11), 1.88 (3H, s, H-14), 1.77 (3H, s, H-15); 13C NMR (DMSO-d6, 150 MHz) δC 163.3 (C-2), 108.9 (C-3), 183.3 (C-4), 159.9 (C-5), 95.8 (C-6), 163.0 (C-7), 107.8 (C-8), 160.6 (C-9), 104.2 (C-10), 109.7 (C-1'), 154.5 (C-2'), 104.8 (C-3'), 162.8 (C-4'), 107.4 (C-5'), 130.5 (C-6'), 22.2 (C-11), 123.2 (C-12), 132.1 (C-13), 26.3 (C-14), 18.6 (C-15)。以上数据文献[22]对照后基本一致, 故鉴定为8-(γ, γ-dimethylallyl)-5, 2', 4'-trihydroxy-7-methoxyflavone。
化合物7 黄色无定形粉末(甲醇), 10%浓硫酸-乙醇溶液喷雾后加热显黄色。ESI-MS m/z 421.16 [M-H]-; 1H NMR (CD3OD, 600 MHz) δH 6.90 (1H, d, J = 8.3 Hz, H-6'), 6.45 (1H, d, J = 2.1 Hz, H-8), 6.27 (1H, d, J = 8.3 Hz, H-5'), 6.17 (1H, d, J = 2.1 Hz, H-6), 5.26 (1H, m, H-17), 5.10 (1H, m, H-12), 3.38 (2H, d, J = 7.0 Hz, H-16), 3.08 (2H, d, J = 7.0 Hz, H-11), 1.78 (3H, s, H-19), 1.67 (3H, s, H-20), 1.57 (3H, s, H-14), 1.33 (3H, s, H-15); 13C NMR (CD3OD, 150 MHz) δC 163.2 (C-2), 122.1 (C-3), 183.7 (C-4), 163.6 (C-5), 99.5 (C-6), 165.5 (C-7), 94.6 (C-8), 159.3 (C-9), 105.5 (C-10), 113.8 (C-1'), 154.7 (C-2'), 117.7 (C-3'), 159.0 (C-4'), 108.1 (C-5'), 128.8 (C-6'), 24.8 (C-11), 122.6 (C-12), 132.8 (C-13), 17.6 (C-14), 25.9 (C-15), 23.3 (C-16), 124.0 (C-17), 131.9 (C-18), 18.0 (C-19), 26.0 (C-20)。以上数据与文献[23]对照后基本一致, 故鉴定为桑皮酮T。
化合物8 黄色无定形粉末(甲醇), 10%浓硫酸-乙醇溶液喷雾后加热显黄色。ESI-MS m/z 337.11 [M-H]-; 1H NMR (CD3OD, 600 MHz) δH 7.78 (2H, d, J = 8.3 Hz, H-2', 6'), 6.92 (2H, d, J = 8.3 Hz, H-3', 5'), 6.54 (1H, s, H-3), 6.46 (1H, s, H-8), 5.24 (1H, m H-12), 3.30 (2H, d, J = 7.4, H-11), 1.78 (3H, s, H-14), 1.66 (3H, s, H-15); 13C NMR (CD3OD, 150 MHz) δC 163.7 (C-2), 103.7 (C-3), 183.9 (C-4), 162.6 (C-5), 113.2 (C-6), 165.9 (C-7), 94.1 (C-8), 157.2 (C-9), 105.1 (C-10), 123.3 (C-1'), 129.3 (C-2', 6'), 117.0 (C-3', 5'), 159.9 (C-4'), 22.3 (C-11), 123.4 (C-12), 132.1 (C-13), 17.9 (C-14), 26.0 (C-15)。以上数据与文献[24]对照后基本一致, 故鉴定为6-(3-methylbut-2-enyl) apigenin。
化合物9 棕黄色无定形粉末(甲醇), 10%浓硫酸-乙醇溶液喷雾后加热显黄色。ESI-MS m/z 353.10 [M-H]-; 1H NMR (CD3OD, 600 MHz) δH 7.89 (1H, d, J = 8.8 Hz, H-6'), 7.12 (1H, s, H-8), 6.64 (1H, overlap, H-3'), 6.63 (1H, s, H-3), 6.57 (1H, dd, J = 8.8, 2.3 Hz, H-5'), 5.32 (2H, m, H-12), 3.35 (2H, d, J = 7.1 Hz, H-11), 1.87 (3H, s, H-14), 1.77 (3H, s, H-15); 13C NMR (CD3OD, 150 MHz) δC 162.4 (C-2), 104.2 (C-3), 182.8 (C-4), 159.6 (C-5), 109.6 (C-6), 162.6 (C-7), 94.0 (C-8), 156.0 (C-9), 104.3 (C-10), 111.5 (C-1'), 159.2 (C-2'), 107.7 (C-3'), 109.0 (C-5'), 130.7 (C-6'), 21.9 (C-11), 123.3 (C-12), 131.5 (C-13), 18.6 (C-14), 26.4 (C-15)。以上数据与文献[25]对照后基本一致, 故鉴定为5, 7, 2', 4'-四羟基-6-异戊烯基黄酮。
化合物10 浅黄色无定形粉末(甲醇), 10%浓硫酸-乙醇溶液喷雾后加热显黄色。ESI-MS m/z 353.10 [M-H]-; 1H NMR (CD3OD, 600 MHz) δH 7.06 (1H, d, J = 8.2 Hz, H-6'), 6.41 (1H, d, J = 2.0 Hz, H-3'), 6.39 (1H, dd, J = 2.0, 8.2 Hz, H-5'), 6.26 (1H, d, J = 2.2 Hz, H-8), 6.17 (1H, d, J = 2.2 Hz, H-6), 5.10 (1H, m, H-12), 3.08 (2H, d, J = 7.0 Hz, H-11), 1.58 (3H, s, H-14), 1.38 (3H, s, H-15); 13C NMR (CD3OD, 150 MHz) δC 159.8 (C-2), 121.9 (C-3), 183.7 (C-4), 163.2 (C-5), 99.5 (C-6), 165.5 (C-7), 94.5 (C-8), 157.7 (C-9), 105.4 (C-10), 113.4 (C-1'), 161.9 (C-2'), 103.7 (C-3'), 163.5 (C-4'), 107.9 (C-5'), 132.4 (C-6'), 24.9 (C-11), 122.8 (C-12), 132.7 (C-13), 25.9 (C-14), 17.6 (C-15)。以上数据与文献[26]对照后基本一致, 故鉴定为albanin A。
3 CatK抑制活性筛选采用荧光比色法对所有化合物进行了抑制CatK活性筛选, 实验流程见本课题组以前的研究[27]。
[1] | Li SZ. Compendium of Materia Medica (本草纲目)[M]. Beijing: People's Medical Publishing House, 1975: 2096-2097. |
[2] | Jia MR, Zhang Y. Chinese National Medicine Dictionary (中国民族药辞典)[M]. Beijing: China Medical Science Press of, 2015: 88. |
[3] | Nomura T, Hano Y, Aida M, et al. Artonins A and B, two new prenylflavonoes from the root bark of Artocarpus heterophyllus L.[J]. Heterocycles, 1989, 29: 1447–1453. DOI:10.3987/COM-89-5019 |
[4] | Yu MH, Zhao T, Yan GR, et al. New isoprenylated flavones and stilbene derivative from Artocarpus hypargyreus[J]. Chem Biodivers, 2012, 9: 394–402. DOI:10.1002/cbdv.v9.2 |
[5] | Di X, Wang S, Wang B, et al. New phenolic compounds from the twigs of Artocarpus heterophyllus[J]. Chin Chem Lett, 2017, 7: 24–28. |
[6] | Zheng ZP, Xu Y, Qin C, et al. Characterization of antiprolif-erative activity constituents from Artocarpus heterophyllus[J]. J Agric Food Chem, 2014, 62: 5519–5527. DOI:10.1021/jf500159z |
[7] | Wei BL, Weng JR, Chiu PH, et al. Antiinflammatory flavonoids from Artocarpus heterophyllus and Artocarpus communis[J]. J Agric Food Chem, 2005, 53: 3867–3871. DOI:10.1021/jf047873n |
[8] | Ko FN, Cheng ZJ, Lin CN, et al. Scavenger and antioxidant properties of prenylflavones isolated from Artocarpus hetero-phyllus[J]. Free Radical Biol Med, 1998, 25: 160–168. DOI:10.1016/S0891-5849(98)00031-8 |
[9] | Ren G, Peng JB, Liu AH, et al. Structure elucidation and NMR assignments of two new flavanones from the roots of Artocarpus heterophyllus[J]. Magn Reson Chem, 2015, 53: 872–874. DOI:10.1002/mrc.4285 |
[10] | Nguyen NT, Nguyen MH, Nguyen HX, et al. Tyrosinase inhibitors from the wood of Artocarpus heterophyllus[J]. J Nat Prod, 2012, 75: 1951–1955. DOI:10.1021/np300576w |
[11] | Mukherjee K, Chattopadhyay N. Pharmacological inhibition of cathepsin K:a promising novel approach for postmeno-pausal osteoporosis therapy[J]. Biochem Pharmacol, 2016, 117: 10–19. DOI:10.1016/j.bcp.2016.04.010 |
[12] | Chapurlat R. Cathepsin K inhibitors and antisclerostin anti-bodies[J]. Joint Bone Spine, 2016, 83: 254–256. DOI:10.1016/j.jbspin.2015.09.008 |
[13] | Yuan WJ, Yuan JB, Peng JB, et al. Flavonoids from the roots of Artocarpus heterophyllus[J]. Fitoterapia, 2017, 117: 133–137. DOI:10.1016/j.fitote.2017.01.016 |
[14] | Zhai XX, Xiao CY, Jiang W, et al. Isoprenylatedphenolics from roots of Artocarpus heterophyllus[J]. Nat Prod Comm, 2017, 12: 921–924. |
[15] | Jia SS, Liu D, Zheng XP, et al. Ten prenylated flavonoids were isolated from liquorice[J]. Acta Pharm Sin (药学学报), 1993, 28: 28–31. |
[16] | Huang CS, Liu HX, Shi JC, et al. Total syntheses of 5, 7-dihydroxy-3-isopentenylflavone and 5-hydroxy-3-isopentenyl-flavone natural compounds[J]. Chem J Chin Univ (高等学校化学学报), 2012, 33: 1978–1983. |
[17] | Rao AVR, Varadan M, Venkataraman K. Colouring matters of the wood of Artocarpus heterophyllus:Part Ⅵ-cyclo-heterophyllin, a flavone linked to three isoprenoid groups[J]. Indian J Chem, 1971, 9: 7–13. |
[18] | Nomura T, Hano Y, Aida M, et al. Artonins A and B, two new prenylflavonoes from the root bark of Artocarpus hetero-phyllus L.[J]. Heterocycles, 1989, 29: 1447–1453. DOI:10.3987/COM-89-5019 |
[19] | Ko HH, Lu YH, Yang SZ, et al. Cytotoxic prenylflavonoids from Artocarpus elasticus[J]. J Nat Prod, 2005, 68: 1692–1695. DOI:10.1021/np050287j |
[20] | Syah YM, Achmad SA, Ghisalberti EL, et al. Artoindone-sianins Q-T, four isoprenylated flavones from Artocarpus champeden Spreng. (Moraceae)[J]. Phytochemistry, 2002, 34: 949–953. |
[21] | Nomura T, Hano Y, Matsumoto Y, et al. Cudraflavones C and D, two new prenylflavones from the root bark of Cudrania tricuspidata (Carr.) Bur.[J]. Heterocycles, 1990, 31: 1339–1344. DOI:10.3987/COM-90-5416 |
[22] | Lin CN, Lu CM, Huang PL. Flavonoids from Artocarpus heterophyllus[J]. Phytochemistry, 1995, 39: 1447–1451. DOI:10.1016/0031-9422(95)00135-T |
[23] | Fukai T, Hano Y, Hirakura K, et al. Structures of a novel 2-arylbenzofuran derivative and two flavone derivatives from the cultivated mulberry tree (Morus lhou Koidz.)[J]. Chem Pharm Bull, 1985, 33: 4288–4295. DOI:10.1248/cpb.33.4288 |
[24] | Abegaz BM, Ngadjui BT, Dongo E, et al. Prenylatedchalcones and flavones from the leaves of Dorstenia kameruniana[J]. Phytochemistry, 1998, 49: 1147–1150. DOI:10.1016/S0031-9422(98)00061-2 |
[25] | Monache GD, Scurria R, Vitali A, et al. Two isoflavones and a flavone from the fruits of Maclura pomifera[J]. Phytochemistry, 1994, 37: 893–898. DOI:10.1016/S0031-9422(00)90379-0 |
[26] | Ren G, Xiang HY, Hu ZC, et al. Chemical constituents from the root bark of Artocarpus styracifolius Pierre[J]. Chin J New Drugs (中国新药杂志), 2013, 22: 1700–1703. |
[27] | Lin QH, Yuan JB, Ma ZL, et al. Isoprenylated flavonoids from roots of Artocarpus styracifolius[J]. Nat Prod Comm, 2016, 11: 1843–1846. |