Molecular Docking and PLIF Studies of Novel Tacrine-Naphtoquinone Hybrids Based on Multi-Target-Directed Ligand Approach for Alzheimer’s Disease

Abstract

Alzheimer's disease (AD), the most typical type of dementia and memory loss, is a complicated and progressive neurodegenerative disorder. Due to the multi-factorial etiology of AD, the multi-target-directed ligand (MTDL) approach can be a potential method in seeking new drug candidates for this disease. In this study, over 200 tacrine-naphtoquinone hybrids have been designed and their drug-likeness, molecular docking, and descriptor analysis were conducted to find out a drug candidate with less toxicity and better binding affinity than tacrine. The Docking analysis was conducted using human acetylcholineesterase (1ACJ), human butyrylcholineesterase (4BDS), and β-secretase (BACE1) (1w51) enzymes using Autodock 4.2 and Vina. Promising results were obtained on the types of interactions. Based on molecular docking on 3 targets as well as protein ligand interaction fingerprint (PLIF) studies, the compounds with better results were introduced as good candidates for synthesis. The validity of docking protocols was confirmed using a set of familiar active ligands and decoys on these targets by means of 2 known statistical metrics such as the receiver-operating characteristic (ROC) and Enrichment Factor (EF). Structure activity relationship (SAR) studies, in these class of compounds, show that the hydroxyethylamine, as a linker, is an essential group to improving binding site to AChE and BACE-1 targets.

Structure-Based Virtual Screening and In Vitro Evaluation of New Trypanosoma cruzi Cruzain Inhibitors

“…The grouping analysis of 2221 ligands made with AuPosSOM showed 20 groups (Figure S1). No grouping pattern correlated with the binding energy, a finding similar to that reported by Fereidoonnezhad et al [25]. In the present work, we selected compounds with the highest binding energy within each clade and reviewed their commercial availability, as previously done in [26].…”

Predicting Cytotoxicity and Enzymatic Activity of Diverse Chemicals Using Goldfish Scale Tissue and Topminnow Hepatoma Cell Line‐based Data

“…reported presence of Broto‐Moreau autocorrelation descriptors to explain cytotoxicity of phenylindole derivatives (antimitotic agents) for two breast cancer cell lines. Additionally, anti‐proliferative activity of n ‐phenyl ureidobenzenesulfonate derivatives against human breast adenocarcinoma (MCF‐7) cell line was also explained with similar descriptors …”

Computational Evaluation of Phytochemical Constituents From Malus Pumila (Apple) for Breast Cancer Treatment

“…The ADMET (absorption, distribution,metabolism, excretion and toxicity was performed using SWISS-ADME (http://www.swissadme.ch/), drug-like properties for the selected ligands were done using QED (Quantitative Estimation of Drug-likeness) https://webs.iiitd. edu.in/oscadd/qed/submit_virtual.php# '' [11]. The ligands which obey the Lipinski rule of five [15] are used for further docking analysis.…”

“…As a result, docking is critical in rational drug design. Given the biological and pharmacological significance of molecular docking, major efforts have been made to improve docking prediction algorithms'' [11].In this work, the potency of the protein EGFR was assessed using in-silico docking with the apple phytochemical constituents.…”