Isoquinoline Alkaloids from Berberis vulgaris as Potential Lead Compounds for the Treatment of Alzheimer's Disease

被引：72

作者：

Hostalkova, Anna ^{[1
]}

Marikova, Jana ^{[2
]}

Opletal, Lubomir ^{[1
]}

Korabecny, Jan ^{[3
,4
]}

Hulcova, Daniela ^{[1
,5
]}

Kunes, Jiri ^{[2
]}

Novakova, Lucie ^{[6
]}

Perez, Daniel I. ^{[7
]}

Jun, Daniel ^{[3
]}

Kucera, Tomas ^{[3
]}

Andrisano, Vincenza ^{[8
]}

Siatka, Tomas ^{[5
]}

Cahlikova, Lucie ^{[1
]}

机构：

[1] Charles Univ Prague, Fac Pharm, Dept Pharmaceut Bot, ADINACO Res Grp, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic

[2] Charles Univ Prague, Fac Pharm, Dept Organ & Bioorgan Chem, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic

[3] Dept Toxicoloxy & Mil Pharm, Trebesska 1575, Hradec Kralove 50005, Czech Republic

[4] Univ Hosp Hradec Kralove, Biomed Res Ctr, Sokolska 581, Hradec Kralove 50005, Czech Republic

[5] Charles Univ Prague, Fac Pharm, Dept Pharmacognosy, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic

[6] Charles Univ Prague, Fac Pharm, Dept Analyt Chem, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic

[7] CSIC, Ctr Invest Biol, Ave Ramiro de Maeztu 9, Madrid 28040, Spain

[8] Univ Bologna, Dept Life Qual Studies, Corso DAugusto 237, I-47921 Rimini, Italy

来源：

JOURNAL OF NATURAL PRODUCTS | 2019年 / 82卷 / 02期

关键词：

PROLYL OLIGOPEPTIDASE; ACETYLCHOLINESTERASE; INHIBITORS; CHOLINESTERASES; DRUGS; BUTYRYLCHOLINESTERASE; OPTIMIZATION; SPECTROSCOPY; DERIVATIVES; ATTENTION;

D O I：

10.1021/acs.jnatprod.8b00592

中图分类号：

Q94 [植物学];

学科分类号：

071001 [植物学];

摘要：

Three new alkaloids, bersavine (3), muraricine (4), and berbostrejdine (8), together with seven known isoquinoline alkaloids (1-2, 5-7, 9, and 10) were isolated from an alkaloidal extract of the root bark of Berberis vulgaris. The structures of the isolated compounds were determined by spectroscopic methods, including 1D and 2D NMR techniques, HRMS, and optical rotation, and by comparison a of the obtained data with those in the literature. The NMR data of berbamine (5), aromoline (6), and obamegine (7) were completely assigned employing 2D NMR experiments. Alkaloids isolated in sufficient amounts were evaluated for their in vitro acetylcholinesterase, butyrylcholinesterase (BuChE), prolyl oligopeptidase, and glycogen synthase kinase-3 beta inhibitory activities. Selected compounds were studied for their ability to permeate through the blood-brain barrier. Significant human BuChE (hBuChE) inhibitory activity was demonstrated by 6 (IC50 = 0.82 +/- 0.10 mu M). The in vitro data were further supported by computational analysis that showed the accommodation of 6 in the active site of hBuChE.

引用

页码：239 / 248

页数：10

共 61 条

[1]

[Anonymous], 2017, SUNSCR MON VERS 2 0

[2]

[Anonymous], 2016, DISC STUD VIS V 17 2

[3]

Prolyl oligopeptidase and its role in the organism: attention to the most promising and clinically relevant inhibitors [J].