Molecular interactions of an alkaloid euchrestifoline as a new acetylcholinesterase inhibitor

Fazal Ur Rehman,- Roohullah Roohullah,Muhammad Faird Khan,Inamullah Khan

doi:10.3329/bjp.v8i4.16417

Abstract

Acetylcholinesterase (AChE) inhibitors are well established therapeutic agents for clinical management of Alzheimer's Diseases and other disorders associated with deficient cholinergic neurotransmission. In the current investigation, a new inhibitor has been reported for its significant AChE inhibitory. euchrestifoline was isolated from the extract of Murraya paniculata. Isolated compound showed significant enzyme inhibitory activity (IC50 value: 93.1 ± 0.0 ?M). Molecular docking revealed structural insights behind its significant inhibitory activity. Various molecular interaction were found between euchrestifoline and Ache especially Ser122, Trp84 and Tyr121. This study indicated promising potential of euchrestifoline to be further developed and explored as potential lead compound.

Highlights

Murraya paniculata (Orange jasmine) is an evergreen shrub, belongs to family Rutaceae
The actual hydrolysis of acetylcholine occurs at the very bottom of the gorge, where four main catalytic subsites; the “Esteratic (ES)”, the “oxyanion hole (OX)”, the “Anionic (AS), termed as choline binding subsite or hydrophobic subsite)” and the “Acyl Pocket (AP)” subsites exists
The ES possesses the catalytic machinery of the enzyme which is dependent on a catalytic triad of Ser200–His440–Glu327 (Harel et al, 1996) while the OX comprise of Gly118, Gly119 and Ala201 (Khan et al, 2010; Szegletes et al, 1998; Zhang et al, 2002)

Summary

Introduction

Murraya paniculata (Orange jasmine) is an evergreen shrub, belongs to family Rutaceae. It is native to southwest Asia like Pakistan, India and China, and found in Indonesian, Brazil, and Philippines. In traditional system of treatment, different parts of the plant are frequently used for multiple purposes. Roots and leaves are used for their analgesic, cough, and effectiveness against hysteria. The antibacterial activity of the plant is documented (Sastri, 1962). It is used for the treatment of various skin disorders, stomachache, and dysentery (Kinoshita et al, 1985). Murranganone and paniculatin from the leaves of Murraya paniculata, have been found to be moderate inhibitors of cholinesterase

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