Synthesis, Molecular Docking, Molecular Dynamics Studies, and Biological Evaluation of 4H-Chromone-1,2,3,4-tetrahydropyrimidine-5-carboxylate Derivatives as Potential Antileukemic Agents

Journal of Chemical Information and Modeling
Zahra DolatkhahSoroush Sardari

Abstract

A series of 4H-chromone-1,2,3,4-tetrahydropyrimidine-5-carboxylates derivatives were synthesized via a three component one-pot condensation of chromone-3-carbaldehyde, alkyl acetoacetate, and urea or thiourea, using MCM-41-SO3H as efficient nanocatalysts and evaluated for their anticancer activity using a combined in silico docking and molecular dynamics protocol to estimate the binding affinity of the title compounds with the Bcr-Abl oncogene. Two programs, AutoDock 4 and AutoDock Vina software were applied to dock the target protein with synthesized compounds and ATP. AutoDock runs resulted in binding energy scores from -7.8 to -10.16 kcal/mol for AutoDock 4 and -6.9 to -8.5 (kcal/mol) for AutoDock Vina. Furthermore, molecular dynamics (MD) simulations are performed using Gromacs for up to 20 ns simulation time investigating the stability of a ligand-protein complex. Finally, a theoretical experiment using MD simulation for 10 ns was performed without defining the initial coordinates, and the affinity binding of ligand to receptors was directly studied, which revealed that the ligand approaches the active sites. The relative free binding energy for the structure 06 (S06), which has the highest binding energy in Autodock 4 and...Continue Reading

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Citations

Feb 15, 2018·Computational and Mathematical Methods in Medicine·Xiangyu ZhangMaosheng Cheng
Aug 25, 2020·Pharmaceutical Chemistry Journal·Noor Ul Amin MohsinUsman Saleem
Aug 8, 2019·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Avinash MishraAbdul Sattar
Nov 16, 2019·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Ana Carolina Fradique de LyraJosué Carinhanha Caldas Santos
Apr 29, 2020·Journal of Biomolecular Structure & Dynamics·Muhammad JunaidDong-Qing Wei
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