In Silico Molecular Docking Analysis of Potential Anti-Alzheimer's Compounds Present in Chloroform Extract of Carissa carandas Leaf Using Gas Chromatography MS/MS

Background: The current treatment of Alzheimer's disease (AD) is far from adequate. AD can be treated by inhibiting either β-amyloid protein deposition or acetylcholinesterase enzyme activity. Many treatments for AD are directed at these 2 targets. In the present study, the phytoconstituents of Carissa carandas chloroform leaf extract were identified by gas chromatography-MS/MS analysis, and in silico molecular docking studies were performed to evaluate their potential against AD. Objectives: The present study aimed to identify the possible anti-Alzheimer's activity of novel phytoconstituents isolated from C carandas. Methods: The powdered leafy material was subjected to successive Soxhlet extraction using 3 different solvents: n-hexane, chloroform, and methanol. The chloroform extract was subjected to gas chromatography-MS/MS analysis, and the observed chromatogram revealed the presence of 48 chemical constituents. Among them, 42 new phytoconstituents are reported in this plant for the first time. The gas chromatography-MS/MS–identified phytoconstituents were evaluated by iGEMDOCK software against AD targets of β-amyloid fibril (protein data bank ID: 2LMN) and recombinant human acetylcholinesterase (protein data bank ID: 3LII) ligands, and their anti-AD potential were compared with those of known inhibitors of galantamine and curcumin. Results: On the basis of results from both docking assays, the 5 compounds with the highest docking energy were further analyzed using in silico admetSAR web portal modeling for the evaluation of parameters such as intestinal absorption, blood-brain barrier permeation, carcinogenicity, and acute oral toxicity. Conclusions: The chloroform leaf extract of C carandas was found to contain constituents that have affinities for the 2 targets tested; that is, amyloid β and acetylcholinesterase. The best docking scores were found for 7 compounds: 1-heneicosanol; N-nonadecanol-1; cholesta-4,6-dien-3-ol, (3beta); di-n-octyl phthalate; 7,9-di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione; 6-undecyl-5,6-dihydro-2H-pyran-2-one, and phenol, 2,4-di-t-butyl-6-nitro compounds, and these compounds were therefore suggested to be promising anti-AD lead compounds. Further, the target leads were subjected to ligplot analysis for their 2-dimensional representation of hydrogen bonding and hydrophobic interactions. Thus, the results obtained from the in silico study of C carandas leaf extract using these computational approaches indicate the presence of phytoconstituents that have affinities for the selected 2 targets of AD. (Curr Ther Res Clin Exp. 2020; 81:XXX–XXX)