CN103497091B - 一种具酪氨酸酶抑制活性的化合物及其制备方法 - Google Patents
一种具酪氨酸酶抑制活性的化合物及其制备方法 Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/205—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings
- C07C39/21—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings with at least one hydroxy group on a non-condensed ring
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- A23B—PRESERVING, e.g. BY CANNING, MEAT, FISH, EGGS, FRUIT, VEGETABLES, EDIBLE SEEDS; CHEMICAL RIPENING OF FRUIT OR VEGETABLES; THE PRESERVED, RIPENED, OR CANNED PRODUCTS
- A23B7/00—Preservation or chemical ripening of fruit or vegetables
- A23B7/14—Preserving or ripening with chemicals not covered by groups A23B7/08 or A23B7/10
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Abstract
本发明公开了一种具酪氨酸酶抑制活性的化合物及其制备方法,属于医药领域。本发明将菠萝蜜木材经95%乙醇超声提取后,浓缩、大孔树脂分离、洗脱、洗脱液浓缩干燥,再用硅胶、凝胶柱层析或制备液相继续分离,收集溶液,浓缩干燥后得样品并进行结构鉴定,得到了具有酪氨酸酶抑制活性的多酚类化合物2-geranyl-2',3,4',5-tetrahydroxy-tran-stilbene。本发明提供的化合物能够有效用于果蔬的酶促褐变的抑制、美白化妆品以及制备用于预防和治疗黑色素过多导致的人体色素沉着性疾病、黑色素瘤以及其他需要抑制酪氨酸酶活性的药物制剂。
Description
技术领域
本发明涉及一种具酪氨酸酶抑制活性的化合物及其制备方法,属于医药领域。
背景技术
酪氨酸酶作为黑色素合成的关键酶,其表达和活性与果蔬的褐变和人体色素沉着性疾病密切相关。因此,酪氨酸酶抑制剂可作为黑色素抑制剂应用于食品、化妆品、医药等领域。
波罗蜜,又称大树菠萝或木波罗,是桑科波罗蜜属常绿乔木,在海南,广西,广东,云南等地有种植。是我国南亚热带著名的特产水果之一,其果大而美观,味极甜,香气浓郁。现代药理学研究表明,从该植物中获得的一些成分具有抗炎、抗氧化、抑制黑色素生物合成、抑制血小板聚集等诸多药理作用。波罗蜜的木材化学成分有黄酮、萜类、二苯乙烯类、长链脂肪酸类等。前面我们发现一类2',4'-二羟基取代的黄酮类化合物普遍具有较强的酪氨酸酶抑制活性,作为后续的研究,最近我们又陆续发现一些具有较强酪氨酸酶抑制活性的新化合物和新天然产物。
发明内容
本发明的目的在于提供一种具酪氨酸酶抑制活性的化合物,是从波罗蜜(Artocarpusheterophyllus)木材中提取的一种具有酪氨酸酶抑制活性的多酚类化合物,是2-香叶基取代-2',3,4',5-四羟基取代反式二苯乙烯(2-geranyl-2',3,4',5-tetrahydroxy-tran-stilbene),其结构式如式Ⅰ所示。
本发明的另外一个目的是提供所述酪氨酸酶抑制活性化合物的制备方法,通过以下步骤实现:
(1)波罗蜜木材用95%(v/v)乙醇超声提取,提取液减压浓缩至干燥物,称重;
(2)提取物用95%(v/v)乙醇溶解,定性滤纸过滤;
(3)所得过滤液与Amberlite XAD16以质量比1:2混合,减压浓缩至干;
(4)将上述混合物上大孔树脂,先后分别用20%、40%、60%、80%、95%乙醇洗脱;
(5)步骤(4)收集60%乙醇洗脱部分6个体积,浓缩得干燥样品,称重,经Sephadex LH-20凝胶柱层析、制备型高效液相色谱分离即得2-geranyl-2',3,4',5-tetrahydroxy-tran-stilbene。
本发明所提供的具有酪氨酸酶抑制活性的化合物可应用于制备抗果蔬酶促褐变抑制剂、化妆品美白剂、预防和治疗黑色素异常导致的人体色素沉着性疾病、黑色素瘤以及其他需要抑制酪氨酸酶活性的病症的药物中,可以作为活性成分,不加或加入食品添加剂辅料、化妆品辅料或药剂上接受的辅料,按照相应剂型的制备方法制成制剂。
所述的剂型包括固体粉末、水溶液、醇溶液、乳液、面膜、巴布剂、注射液、滴注液、粉针剂、颗粒剂、片剂、冲剂、散剂、口服液、糖衣剂、薄膜衣片剂、肠溶衣片剂、胶囊剂、硬胶囊剂、软胶囊剂、***剂、颗粒剂、丸剂、膏剂、丹剂、喷雾剂、滴丸剂、崩解剂、口崩剂、微丸等。
本发明的有益之处在于:提供一种波罗蜜木材中提取的具有酪氨酸酶抑制活性的多酚类化合物具有比阳性对照物曲酸更强的活性,制成相应制剂易于质量控制,可应用在抗果蔬酶促褐变抑制剂、化妆品美白剂、预防和治疗黑色素异常导致的人体色素沉着性疾病、黑色素瘤以及其他需要抑制酪氨酸酶活性的病症的药物中。
附图说明
图1为化合物2-geranyl-2',3,4',5-tetrahydroxy-tran-stilbene的1H NMR谱
图2为化合物2-geranyl-2',3,4',5-tetrahydroxy-tran-stilbene的13C NMR谱
具体实施方式
实施例1 2-geranyl-2',3,4',5-tetrahydroxy-tran-stilbene的制备
将20kg波罗蜜木材用6倍质量的95%(v/v)乙醇超声波(50Hz,250w)提取2次,每次1h,减压浓缩至干燥,称重。取适量干燥物用95%乙醇溶解(只要能溶解就行,无需精确比例),定性滤纸过滤,所得过滤液与Amberlite XAD16以质量比1:2混合,自然晾干或减压蒸干,然后上Amberlite XAD16大孔树脂层析,分别用20%、40%、60%、80%、95%(v/v)乙醇洗脱6个柱体积,收集洗脱液,分别减压回收乙醇至干。将所收集的60%(v/v)乙醇洗脱部分的浓缩干燥样品称重,用凝胶柱层析(Sephadex LH-20)进行分离,正己烷-乙酸乙酯(v/v:3/1)洗脱,得到六个流分(流分A-F),流分C进一步凝胶柱层析(Sephadex LH-20),甲醇-水(v/v:1/1)洗脱,收集洗脱液然后用制备的高效液相色谱(Waters制备型高效液相色谱仪,双波长检测器,制备柱为YMC250mm*20mm、粒度为5u)分离,检测波长为254nm,60%甲醇等梯度洗脱即得。
2-geranyl-2',3,4',5-tetrahydroxy-tran-stilbene的核磁共振光谱数据如下:
1H NMR(Acetone-d6,400MHz)δ:8.60(1H,OH),8.42(1H,OH),8.15(1H,OH-3),7.98(1H,OH),7.38(1H,d,J=8.8Hz,H-6'),7.23(2H,s,H-7',8'),6.66(1H,d,J=2.4Hz,H-6),6.44(1H,d,J=2.4Hz,H-3'),6.38(1H,dd,J=8.4,2.4Hz,H-5'),6.33(1H,d,J=2.4Hz,H-4),5.22(1H,m,H-7''),5.19(1H,m,H-2''),3.45(2H,d,J=6.4Hz,H-1''),2.28(1H,d,J=7.2Hz,H-5''),2.25(1H,d,J=7.2Hz,H-4''),2.16(1H,d,J=7.2Hz,H-4''),2.12(1H,d,J=7.2Hz,H-5''),1.67(3H,br s,H-8''),1.66(3H,br s,9''),1.62(3H,br s,H-10'');13C NMR(Acetone-d6,100MHz)δ:159.1(C,C-4'),157.0(C,C-2'),156.9(C,C-3),156.8(C,C-5),140.1(C,C-1),134.6(C,C-3''),131.9(C,C-7''),128.3(CH,C-6'),126.1(CH,C-2''),125.6(CH,C-7'),125.5(CH,C-6''),124.5(CH,C-8'),118.4(C,C-2),117.7(C,C-1'),108.5(CH,C-5'),104.3(CH,C-6),103.8(CH,C-3'),102.5(CH,C-4),33.0(CH2,C-5''),27.3(CH2,C-4''),26.0(CH3,C-8''),24.8(CH2,C-1''),23.8(CH3,C-10''),17.8(CH3,C-9'')。
ESI-MS:m/z379.2[M-H]-,403.3[M+Na]+(C24H28O4)。
结构解析表明该化合物为2-geranyl-2',3,4',5-tetrahydroxy-tran-stilbene。
实施例2 酪氨酸酶抑制活性评价方法
将2-geranyl-2',3,4',5-tetrahydroxy-tran-stilbene先用DMSO溶解,然后用磷酸盐缓冲溶液分别配成50、25、10、5、2.5μg/mL。阳性对照曲酸配成50、25、10、5、2.5μg/mL浓度的溶液。取五种浓度的溶液各30μL,用970μL pH6.8的磷酸盐缓冲溶液配成1mL,加进0.1mg/mL的酪氨酸1mL,然后加入由pH值6.8的磷酸盐缓冲溶液配成的1mL酪氨酸酶(200U/mL),在37°C下孵育20min,于490nm处测定吸光值。
酶活性抑制率=[(A2-A1)-(B2-B1)]/(A2-A1)×100%
A1为0min时候未加抑制剂的吸收值;A2为20min后未加抑制剂的吸收值;
B1为0min时候加抑制剂的吸收值;B2为20min后加了抑制剂的吸收值。
实施例3 化合物酪氨酸酶抑制活性评价
2-geranyl-2',3,4',5-tetrahydroxy-tran-stilbene抑制酪氨酸酶的IC50为14.2μM,曲酸的IC50为67.6μM。化合物2-geranyl-2',3,4',5-tetrahydroxy-tran-stilbene的酪氨酸酶抑制活性远远大于曲酸。
虽然本发明已以较佳实施例公开如上,但其并非用以限定本发明,任何熟悉此技术的人,在不脱离本发明的精神和范围内,都可做各种的改动与修饰,因此本发明的保护范围应该以权利要求书所界定的为准。
Claims (5)
1.一种具有酪氨酸酶抑制活性的化合物,其特征在于,所述化合物为2-香叶基取代-2',3,4',5-四羟基取代反式二苯乙烯,其结构式为:
2.一种制备权利要求1所述化合物的方法,其特征在于,通过以下步骤实现:
(1)波罗蜜木材用95%乙醇超声提取,提取液减压浓缩至干燥物,称重;
(2)提取物用95%乙醇溶解,定性滤纸过滤;
(3)上述过滤液与Amberlite XAD16以质量比1:2混合,减压浓缩至干;
(4)将上述混合物上大孔树脂,先后分别用20%、40%、60%、80%、95%乙醇洗脱;
(5)步骤(4)收集60%乙醇洗脱部分6个体积,浓缩得干燥样品,称重,经Sephadex LH-20凝胶柱层析、制备型高效液相色谱分离得到2-香叶基取代-2',3,4',5-四羟基取代反式二苯乙烯。
3.权利要求1所述化合物在果蔬的抗酶促褐变、美白化妆品以及制备用于预防和治疗黑色素过多导致的需要抑制酪氨酸酶活性的病症药物中的应用。
4.根据权利要求3所述的应用,其特征在于,不加抗酶促褐变辅料、化妆品配方、药物制剂辅料。
5.根据权利要求3所述的应用,其特征在于,加入抗酶促褐变辅料、化妆品配方、药物制剂辅料中的一种或多种。
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Non-Patent Citations (2)
Title |
---|
Yeon Mi Kim等.Oxyresveratrol and Hydroxystilbene Compounds.《The Journal of Biological Chemistry》.2002,第277卷第16340-16344页. * |
陈清西等.酪氨酸酶抑制剂的研究进展.《厦门大学学报》.2007,第46卷(第2期),第274-282页. * |
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