Norditerpenoid alkaloids of Delphinium denudatum as cholinesterase inhibitors

被引：33

作者：

Ahmad, Hanif ^{[1
]}

Ahmad, Shujaat ^{[1
,2
]}

Ali, Mumtaz ^{[1
]}

Latif, Abdul ^{[1
]}

Shah, Syed Adnan Ali ^{[3
,4
]}

Naz, Humera ^{[3
,4
]}

Rahman, Najeeb Ur ^{[1
]}

Shaheen, Farzana ^{[5
]}

Wadood, Abdul ^{[6
]}

Khan, Hidayat Ullah ^{[7
]}

Ahmad, Manzoor ^{[1
]}

机构：

[1] Univ Malakand, Dept Chem, Dir L 18550, KP, Pakistan

[2] Shaheed Benazir Bhutto Univ, Dept Pharm, Sheringal Dir U 18000, KP, Pakistan

[3] Univ Teknol MARA, Fac Pharm, Puncak Alam Campus, Bandar Puncak Alam 42300, Selangor De, Malaysia

[4] Univ Teknol MARA, Atta Ur Rahman Inst Nat Prod Discovery AuRIns, Puncak Alam Campus, Bandar Puncak Alam 42300, Selangor De, Malaysia

[5] Univ Karachi, ICCBS, HEJ Res Inst Chem, Karachi, Pakistan

[6] Abdul Wali Khan Univ Mardan, Dept Biochem, Khyber Pakhtunkhwa, Pakistan

[7] Univ Sci & Technol, Dept Biotechnol, Bannu, Khyber Pakhtunk, Pakistan

来源：

BIOORGANIC CHEMISTRY | 2018年 / 78卷

关键词：

Delphinium denudatum; Norditerpenoid alkaloids; X-ray crystallography; Enzyme inhibition activity; DITERPENOID ALKALOIDS; CRYSTAL-STRUCTURE; ACONITUM-LAEVE; ROOTS;

D O I：

10.1016/j.bioorg.2018.04.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Three new norditerpenoids alkaloids, 1 beta-hydroxy, 14 beta-acetyl condelphine (1), jadwarine-A (2), jadwarine-B (3) along with two known alkaloids isotalatizidine hydrate (4) and dihydropentagynine (5) were isolated from medicinal plant Delphinium denudatum. The structures of natural products 1-5 were established on the basis of HR-EIMS, H-1 and C-13 NMR (1D & 2D) spectroscopic data as well as by comparison from literature data. The structures of compound 1 and 4 were also confirmed by single crystal X-ray diffraction studies. In-vitro AChE and BChE enzyme inhibitory activities of compounds 1-5 and molecular docking studies were performed to investigate the possible molecular inhibitory mechanism of the isolated natural products. Compound 2, 4 and 5 showed competitive inhibitory effects by inhibiting AChE and BChE, respectively, while 1 and 3 showed noncompetitive inhibition. This work is the first report that provides a supporting evidence about the use of constituents of Delphinium denudatum in cerebral dementia and Alzheimer diseases.

引用

页码：427 / 435

页数：9

共 23 条

[1] The anti-stress activity of a gem-containing Unani formulation against diverse stressors [J].