磷酸二酯酶天然抑制剂的研究进展
|
摘要
磷酸二酯酶(PDEs)是一类多基因大家族酶,包括11型,可以通过水解细胞内第二信使环磷酸腺苷和环磷酸鸟苷调节细胞内的多种信号传递和生理活动。研究表明,PDEs参与了炎症、抑郁、哮喘等多种病理过程的发生发展,是新药研究的热门靶点。近年来,从天然产物中发现了一些特异性强、活性高的PDEs抑制成分。对PDEs各家族的生物学特点、生理病理学意义及其天然抑制剂的研究进展进行综述,以期为PDEs抑制剂新药的研发提供参考。
Phosphodiesterases(PDEs) represent an important enzyme class constituted by 11 isozymes(PDE1 to PDE11). They can regulate gene expression and nucleotide signaling pathway through the hydrolysis of c AMP and c GMP. Studies showed that PDEs have become one of the most popular research topics in the new drug development because they involved in the development of many pathological processes, such as inflammation, depression, asthma and so on. In recent years, many specific and efficient PDEs inhibitors derived from natural products have been reported. This paper reviews the biochemical properties, physiological functions, and their natural inhibitors of the PDEs families for providing a solid support for the further new drug development of selective PDEs inhibitors.
Phosphodiesterases(PDEs) represent an important enzyme class constituted by 11 isozymes(PDE1 to PDE11). They can regulate gene expression and nucleotide signaling pathway through the hydrolysis of c AMP and c GMP. Studies showed that PDEs have become one of the most popular research topics in the new drug development because they involved in the development of many pathological processes, such as inflammation, depression, asthma and so on. In recent years, many specific and efficient PDEs inhibitors derived from natural products have been reported. This paper reviews the biochemical properties, physiological functions, and their natural inhibitors of the PDEs families for providing a solid support for the further new drug development of selective PDEs inhibitors.
引文
[1]陈昌亮,黄爽.磷酸二酯酶及其抑制剂的研究进展[J].中国药理学通报,2014,30(2):283-286.
[2]Keravis T,Lugnier C.Cyclic nucleotide phosphodiesterase(PDE)isozymes as targets of the intracellular signalling network:Benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments[J].Br J Pharmacol,2012,165(5):1288-1305.
[3]陈玲,徐英,潘建春.磷酸二酯酶参与认知与情绪调节的研究进展[J].中国药理学与毒理学杂志,2012,26(3):357-362.
[4]Garnock-Jones K P.Roflumilast:A review in COPD[J].Drugs,2015,75(14):1645-1656.
[5]Schafer P H,Parton A,Capone L,et al.Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity[J].Cell Signal,2014,26(9):2016-2029.
[6]Qu X Y,Zhang S X,Tao L N,et al.A meta-analysis of apremilast on psoriatic arthritis long-term assessment of clinical efficacy(PALACE)[J].Expert Rev Clin Phar,2016,9(6):799-805.
[7]郭瑞霞,李力更,王于方,等.天然药物化学史话:天然产物化学研究的魅力[J].中草药,2015,46(14):2019-2033.
[8]Kumar A,Singh A,Ekavali.A review on Alzheimer’s disease pathophysiology and its management:An update[J].Pharmacol Rep,2015,67(2):195-203.
[9]胡昌奇.脑血管病治疗药长春胺的研究概况[J].国外医学:药学分册,1979,7(4):219-222.
[10]覃文才,张均田.尼莫地平、硝苯吡啶和长春胺对大鼠与小鼠化学性记忆障碍的改善作用[J].中国医学科学院学报,1986,8(5):366-370.
[11]Ren N,Liu J J,Yang D L,et al.Indentification of vincamine indole alkaloids producing endophytic fungi isolated from Nerium indicum,apocynaceae[J].Microbiol Res,2016,doi:10.1016/j.micres.2016.06.008.
[12]Gupta S,Singh P,Sharma B M,et al.Neuroprotective effects of agomelatine and vinpocetine against chronic cerebral hypoperfusion induced vascular dementia[J].Curr Neurovasc Res,2015,12(3):240-252.
[13]任骞,张杰.长春西汀药理作用机制研究进展[J].中草药,2013,44(11):1517-1520.
[14]Weber S,Zeller M,Guan K,et al.PDE2 at the crossway between c AMP and c GMP signalling in the heart[J].Cell Signal,2017,doi:10.1016/j.cellsig.2017.06.020.
[15]Gomez L,Breitenbucher J G.PDE2 inhibition:Potential for the treatment of cognitive disorders[J].Bioorg MedChem Lett,2013,23(24):6522-6527.
[16]杨楠,贾晓斌,张振海,等.黄酮类化合物抗肿瘤活性及机制研究进展[J].中国中药杂志,2015,40(3):373-381.
[17]赵新筠,陈喜,湛昌国.磷酸二酯酶2(PDE2)结构及其选择性抑制剂的研究进展[J].有机化学,2009,29(2):159-165.
[18]宋笑丹,马满玲.金雀异黄素的药学研究进展及临床应用[J].沈阳药科大学学报,2009(S1):127.
[19]张博,尤启冬,高署.磷酸二酯酶3抑制剂的功能和临床应用[J].安徽医药,2010,14(10):1220-1221.
[20]谭萍,郝勇,刘雁,等.银杏叶提取物单体成分对血小板磷酸二酯酶3活性的作用研究[J].中华临床医师杂志:电子版,2013,7(24):11569-11573.
[21]Chong J,Leung B,Poole P.Phosphodiesterase 4inhibitors for chronic obstructive pulmonary disease[J].Cochrane Database Syst Rev,2017,doi:10.1002/14651858.CD002309.pub4.
[22]Ko W C,Chen M C,Wang S H,et al.3-Omethylquercetin more selectively inhibits phosphodiesterase subtype 3[J].Plant Med,2003,69(4):310-315.
[23]Spadaccini M,D’Alessio S,Peyrin-Biroulet L,et al.PDE4 inhibition and inflammatory bowel disease:A novel therapeutic avenue[J].Int J Mol Sci,2017,18(6):E1276.
[24]Mease P J.Apremilast:A Phosphodiesterase 4 Inhibitor for the treatment of psoriatic arthritis[J].Rheumatol Ther,2014,doi:10.1007/s40744-014-0005-4.
[25]Lin T T,Huang Y Y,Tang G H,et al.Prenylated coumarins:Natural phosphodiesterase-4 inhibitors from Toddalia asiatica[J].J Nat Prod,2014,77(4):955-962.
[26]Zhong J S,Huang Y Y,Zhang T H,et al.Natural phosphodiesterase-4 inhibitors from the leaf skin of Aloe barbadensis Miller[J].Fitoterapia,2015,doi:10.1016/j.fitote.2014.11.018.
[27]Liu Y N,Huang Y Y,Bao J M,et al.Natural phosphodiesterase-4(PDE4)inhibitors from Crotalaria ferruginea[J].Fitoterapia,2014,doi:10.1016/j.fitote.2014.02.010.
[28]Cheng Z B,Deng Y L,Han Q H,et al.Prostaglandin derivatives:Nonaromatic phosphodiesterase-4 inhibitors from the soft coral Sarcophyton ehrenbergi[J].J Nat Prod,2014,770(8):1928-1936.
[29]Huang Y,Liu X,Wu D,et al.The discovery,complex crystal structure,and recognition mechanism of a novel natural PDE4 inhibitor from Selaginella pulvinata[J].Biochem Pharmacol,2017,130(15):51-59.
[30]Coon T A,Mckelvey A C,Weathington N M,et al.Novel PDE4 inhibitors derived from chinese medicine Forsythia[J].PLo S One,2014,9(12):e115937.
[31]Guo Y Q,Tang G H,Lou L L,et al.Prenylated flavonoid as potent phosphodiesterase-4 inhibitors from Morusalba:Isolation,modification,and structure-activity relationship study[J].Eur J Med Chem,2018,144(20):758-766.
[32]Chen S K,Zhao P,Shao Y X,et al.Moracin M from Morus alba L.is a natural phosphodiesterase-4 inhibitor[J].Bioorg Med Chem Lett,2012,22(9):3261-3264.
[33]何细新,罗海彬,谭冰心,等.α-倒捻子素作为磷酸二酯酶4的抑制剂的用途:中国,CN 107224433 A[P].2017-10-03.
[34]姜代勋,陈武,于同泉,等.中草药对磷酸二酯酶4活性影响的初步研究[J].北京农学院学报,2006,21(1):7-9.
[35]蔡颖红,曹志远,谢丽霞,等.10种常用平喘中药对磷酸二酯酶4抑制作用的研究[J].药物评价研究,2012,35(5):345-347.
[36]孙美,王立波,吴立军.药用紫珠属植物的研究进展[J].安徽农业科学,2015,43(13):101-104.
[37]杨璐,张天华,白旭,等.14种紫珠属植物醇提取物抑制磷酸二酯酶4活性初探[J].广东药学院学报,2015,31(3):328-331.
[38]Barone I,Giordano C,Bonofiglio D,et al.Phosphodiesterase type 5 and cancers:Progress and challenges[J].Oncotarget,2017,8(58):99179-99202.
[39]姜睿,吴邦财.PDE5抑制剂治疗ED的不良反应及防治措施[J].中华男科学杂志,2016,11(2):99-103.
[40]辛钟成,田贞姬,林桂婷,等.淫羊藿甙对阴茎海绵体的松弛效应及其作用机制[J].科学通报,2001,46(6):485-489.
[41]饶勇,龚晓华,马卫列,等.磷酸二酯酶7及其抑制剂[J].中国生物化学与分子生物学报,2012,28(10):906-912.
[42]高庆平,吴倩,孟丹丹,等.噻吩并嘧啶酮类PDE7抑制剂的特征结构及作用机制研究[J].化学试剂,2017,39(10):1054-1058.
[43]付源,李佳,孙胜永,等.胡黄连与牛蒡子有效成分对猪磷酸二酯酶7A2活性的影响[J].北京农学院学报,2014,29(4):65-68.
[44]Cheng Z B,Lu X,Bao J M,et al.(±)-Torreyunlignans A-D,rare 8-9′linked neolignan enantiomers as phosphodiesterase-9A inhibitors from Torreyayunnanensis[J].J Nat Prod,2014,77(12):2651-2657.
[45]闫军浩,沈倩诚,王争.磷酸二酯酶10A及其研究进展[J].上海交通大学学报:医学版,2015,35(12):1904-1910.
[46]周恬恬,王林元,王景霞,等.芍药苷对血虚肝郁证大鼠海马磷酸二酯酶不同亚型的影响[J].北京中医药大学学报,2016,39(4):288-292.
[2]Keravis T,Lugnier C.Cyclic nucleotide phosphodiesterase(PDE)isozymes as targets of the intracellular signalling network:Benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments[J].Br J Pharmacol,2012,165(5):1288-1305.
[3]陈玲,徐英,潘建春.磷酸二酯酶参与认知与情绪调节的研究进展[J].中国药理学与毒理学杂志,2012,26(3):357-362.
[4]Garnock-Jones K P.Roflumilast:A review in COPD[J].Drugs,2015,75(14):1645-1656.
[5]Schafer P H,Parton A,Capone L,et al.Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity[J].Cell Signal,2014,26(9):2016-2029.
[6]Qu X Y,Zhang S X,Tao L N,et al.A meta-analysis of apremilast on psoriatic arthritis long-term assessment of clinical efficacy(PALACE)[J].Expert Rev Clin Phar,2016,9(6):799-805.
[7]郭瑞霞,李力更,王于方,等.天然药物化学史话:天然产物化学研究的魅力[J].中草药,2015,46(14):2019-2033.
[8]Kumar A,Singh A,Ekavali.A review on Alzheimer’s disease pathophysiology and its management:An update[J].Pharmacol Rep,2015,67(2):195-203.
[9]胡昌奇.脑血管病治疗药长春胺的研究概况[J].国外医学:药学分册,1979,7(4):219-222.
[10]覃文才,张均田.尼莫地平、硝苯吡啶和长春胺对大鼠与小鼠化学性记忆障碍的改善作用[J].中国医学科学院学报,1986,8(5):366-370.
[11]Ren N,Liu J J,Yang D L,et al.Indentification of vincamine indole alkaloids producing endophytic fungi isolated from Nerium indicum,apocynaceae[J].Microbiol Res,2016,doi:10.1016/j.micres.2016.06.008.
[12]Gupta S,Singh P,Sharma B M,et al.Neuroprotective effects of agomelatine and vinpocetine against chronic cerebral hypoperfusion induced vascular dementia[J].Curr Neurovasc Res,2015,12(3):240-252.
[13]任骞,张杰.长春西汀药理作用机制研究进展[J].中草药,2013,44(11):1517-1520.
[14]Weber S,Zeller M,Guan K,et al.PDE2 at the crossway between c AMP and c GMP signalling in the heart[J].Cell Signal,2017,doi:10.1016/j.cellsig.2017.06.020.
[15]Gomez L,Breitenbucher J G.PDE2 inhibition:Potential for the treatment of cognitive disorders[J].Bioorg MedChem Lett,2013,23(24):6522-6527.
[16]杨楠,贾晓斌,张振海,等.黄酮类化合物抗肿瘤活性及机制研究进展[J].中国中药杂志,2015,40(3):373-381.
[17]赵新筠,陈喜,湛昌国.磷酸二酯酶2(PDE2)结构及其选择性抑制剂的研究进展[J].有机化学,2009,29(2):159-165.
[18]宋笑丹,马满玲.金雀异黄素的药学研究进展及临床应用[J].沈阳药科大学学报,2009(S1):127.
[19]张博,尤启冬,高署.磷酸二酯酶3抑制剂的功能和临床应用[J].安徽医药,2010,14(10):1220-1221.
[20]谭萍,郝勇,刘雁,等.银杏叶提取物单体成分对血小板磷酸二酯酶3活性的作用研究[J].中华临床医师杂志:电子版,2013,7(24):11569-11573.
[21]Chong J,Leung B,Poole P.Phosphodiesterase 4inhibitors for chronic obstructive pulmonary disease[J].Cochrane Database Syst Rev,2017,doi:10.1002/14651858.CD002309.pub4.
[22]Ko W C,Chen M C,Wang S H,et al.3-Omethylquercetin more selectively inhibits phosphodiesterase subtype 3[J].Plant Med,2003,69(4):310-315.
[23]Spadaccini M,D’Alessio S,Peyrin-Biroulet L,et al.PDE4 inhibition and inflammatory bowel disease:A novel therapeutic avenue[J].Int J Mol Sci,2017,18(6):E1276.
[24]Mease P J.Apremilast:A Phosphodiesterase 4 Inhibitor for the treatment of psoriatic arthritis[J].Rheumatol Ther,2014,doi:10.1007/s40744-014-0005-4.
[25]Lin T T,Huang Y Y,Tang G H,et al.Prenylated coumarins:Natural phosphodiesterase-4 inhibitors from Toddalia asiatica[J].J Nat Prod,2014,77(4):955-962.
[26]Zhong J S,Huang Y Y,Zhang T H,et al.Natural phosphodiesterase-4 inhibitors from the leaf skin of Aloe barbadensis Miller[J].Fitoterapia,2015,doi:10.1016/j.fitote.2014.11.018.
[27]Liu Y N,Huang Y Y,Bao J M,et al.Natural phosphodiesterase-4(PDE4)inhibitors from Crotalaria ferruginea[J].Fitoterapia,2014,doi:10.1016/j.fitote.2014.02.010.
[28]Cheng Z B,Deng Y L,Han Q H,et al.Prostaglandin derivatives:Nonaromatic phosphodiesterase-4 inhibitors from the soft coral Sarcophyton ehrenbergi[J].J Nat Prod,2014,770(8):1928-1936.
[29]Huang Y,Liu X,Wu D,et al.The discovery,complex crystal structure,and recognition mechanism of a novel natural PDE4 inhibitor from Selaginella pulvinata[J].Biochem Pharmacol,2017,130(15):51-59.
[30]Coon T A,Mckelvey A C,Weathington N M,et al.Novel PDE4 inhibitors derived from chinese medicine Forsythia[J].PLo S One,2014,9(12):e115937.
[31]Guo Y Q,Tang G H,Lou L L,et al.Prenylated flavonoid as potent phosphodiesterase-4 inhibitors from Morusalba:Isolation,modification,and structure-activity relationship study[J].Eur J Med Chem,2018,144(20):758-766.
[32]Chen S K,Zhao P,Shao Y X,et al.Moracin M from Morus alba L.is a natural phosphodiesterase-4 inhibitor[J].Bioorg Med Chem Lett,2012,22(9):3261-3264.
[33]何细新,罗海彬,谭冰心,等.α-倒捻子素作为磷酸二酯酶4的抑制剂的用途:中国,CN 107224433 A[P].2017-10-03.
[34]姜代勋,陈武,于同泉,等.中草药对磷酸二酯酶4活性影响的初步研究[J].北京农学院学报,2006,21(1):7-9.
[35]蔡颖红,曹志远,谢丽霞,等.10种常用平喘中药对磷酸二酯酶4抑制作用的研究[J].药物评价研究,2012,35(5):345-347.
[36]孙美,王立波,吴立军.药用紫珠属植物的研究进展[J].安徽农业科学,2015,43(13):101-104.
[37]杨璐,张天华,白旭,等.14种紫珠属植物醇提取物抑制磷酸二酯酶4活性初探[J].广东药学院学报,2015,31(3):328-331.
[38]Barone I,Giordano C,Bonofiglio D,et al.Phosphodiesterase type 5 and cancers:Progress and challenges[J].Oncotarget,2017,8(58):99179-99202.
[39]姜睿,吴邦财.PDE5抑制剂治疗ED的不良反应及防治措施[J].中华男科学杂志,2016,11(2):99-103.
[40]辛钟成,田贞姬,林桂婷,等.淫羊藿甙对阴茎海绵体的松弛效应及其作用机制[J].科学通报,2001,46(6):485-489.
[41]饶勇,龚晓华,马卫列,等.磷酸二酯酶7及其抑制剂[J].中国生物化学与分子生物学报,2012,28(10):906-912.
[42]高庆平,吴倩,孟丹丹,等.噻吩并嘧啶酮类PDE7抑制剂的特征结构及作用机制研究[J].化学试剂,2017,39(10):1054-1058.
[43]付源,李佳,孙胜永,等.胡黄连与牛蒡子有效成分对猪磷酸二酯酶7A2活性的影响[J].北京农学院学报,2014,29(4):65-68.
[44]Cheng Z B,Lu X,Bao J M,et al.(±)-Torreyunlignans A-D,rare 8-9′linked neolignan enantiomers as phosphodiesterase-9A inhibitors from Torreyayunnanensis[J].J Nat Prod,2014,77(12):2651-2657.
[45]闫军浩,沈倩诚,王争.磷酸二酯酶10A及其研究进展[J].上海交通大学学报:医学版,2015,35(12):1904-1910.
[46]周恬恬,王林元,王景霞,等.芍药苷对血虚肝郁证大鼠海马磷酸二酯酶不同亚型的影响[J].北京中医药大学学报,2016,39(4):288-292.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |