Ahmad Hanif, Ahmad Shujaat, Khan Ezzat, Shahzad Adnan, Ali Mumtaz, Tahir Muhammad Nawaz, Shaheen Farzana, Ahmad Manzoor
a Department of Chemistry , University of Malakand , Chakdara KP , Pakistan.
b Department of Pharmacy , Shaheed Benazir Bhutto University , Sheringal , KP , Pakistan.
Pharm Biol. 2017 Dec;55(1):680-686. doi: 10.1080/13880209.2016.1240207.
Delphinium denudatum Wall (Ranunculaceae) is a rich source of diterpenoid alkaloids and is widely used for the treatment of various neurological disorders such as epilepsy, sciatica and Alzheimer's disease.
The present study describes crystal structure determination and cholinesterase inhibitory potential of isotalatazidine hydrate isolated from the aerial part of Delphinium denudatum.
Phytochemical investigation of Delphinium denudatum resulted in the isolation of isotalatazidine hydrate in crystalline form. The molecular structure of the isolated compound was established by X-ray diffraction. The structural data (bond length and angles) of the compound were calculated by Density Functional Theory (DFT) using B3LYP/6-31 + G (p) basis set. The cholinesterase inhibitory potential of the isolated natural product was determined at various concentrations (62.5, 125, 250, 500 and 1000 μg/mL) followed by molecular docking to investigate the possible inhibitory mechanism of isotalatazidine hydrate.
The compound crystallized in hexagonal unit cell with space group P6 Some other electronic properties such as energies associated with HOMO-LUMO, band gaps, global hardness, global electrophilicity, electron affinity and ionization potential were also calculated by means of B3LYP/6-31 + G (p) basis set. The compound showed competitive type inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC values of 12.13 μM and 21.41 μM, respectively.
These results suggest that isotalatazidine hydrate is a potent dual cholinesterase inhibitor and can be used as a target drug in Alzheimer diseases. This is first report indicating isotalatazidine hydrate with anticholinesterase potential.
露蕊乌头（毛茛科）是二萜生物碱的丰富来源，被广泛用于治疗各种神经系统疾病，如癫痫、坐骨神经痛和阿尔茨海默病。
本研究描述了从露蕊乌头地上部分分离得到的水合异塔拉他定的晶体结构测定及其胆碱酯酶抑制潜力。
对露蕊乌头进行植物化学研究，得到了结晶形式的水合异塔拉他定。通过X射线衍射确定了分离得到的化合物的分子结构。使用密度泛函理论（DFT），采用B3LYP/6-31+G（p）基组计算了该化合物的结构数据（键长和键角）。在不同浓度（62.5、125、250、500和1000μg/mL）下测定了分离得到的天然产物的胆碱酯酶抑制潜力，随后进行分子对接以研究水合异塔拉他定可能的抑制机制。
该化合物以六方晶胞形式结晶，空间群为P6。还通过B3LYP/6-31+G（p）基组计算了一些其他电子性质，如与最高占据分子轨道-最低未占据分子轨道相关的能量、带隙、全局硬度、全局亲电性、电子亲和能和电离势。该化合物对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）均表现出竞争性抑制，IC值分别为12.13μM和21.41μM。
这些结果表明，水合异塔拉他定是一种有效的双胆碱酯酶抑制剂，可作为治疗阿尔茨海默病的靶向药物。这是首次报道水合异塔拉他定具有抗胆碱酯酶潜力。
