Quantum computational investigations and molecular docking studies on amentoflavone

Abstract

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, with approximately 6-7 million people infected worldwide, becoming a public health problem in tropical countries, thus generating an increasing demand for the development of more effective drugs, due to the low efficiency of the existing drugs. Aiming at the development of a new antichagasic pharmacological tool, the density functional theory was used to calculate the reactivity descriptors of amentoflavone, a biflavonoid with proven antitrypanosomal activity in vitro, as well as to perform a study of interactions with the enzyme cruzain, an enzyme key in the evolutionary process of T-cruzi. Structural properties (in solvents with different values of dielectric constant), the infrared spectrum, the frontier orbitals, Fukui analysis, thermodynamic properties were the parameters calculated from DFT method with the monomeric structure of the apigenin used for comparison. Furthermore, molecular docking studies were performed to assess the potential use of this biflavonoid as a pharmacological antichagasic tool. The frontier orbitals (HOMO-LUMO) study to find the band gap of compound has been extended to calculate electron affinity, ionization energy, electronegativity electrophilicity index, chemical potential, global chemical hardness and global chemical softness to study the chemical behaviour of compound. The optimized structure was subjected to molecular Docking to characterize the interaction between amentoflavone and cruzain enzyme, a classic pharmacological target for substances with anti-gas activity, where significant interactions were observed with amino acid residues from each one's catalytic sites enzyme. These results suggest that amentoflavone has the potential to interfere with the enzymatic activity of cruzain, thus being an indicative of being a promising antichagasic agent.

Insights Into Amentoflavone: A Natural Multifunctional Biflavonoid

“…Molecular docking and molecular dynamics simulation are algorithm-based virtual screening methods searching for candidate drugs or molecules in a short time and serving for experimental studies ( Alonso et al, 2006 ; De Vivo et al, 2016 ; Wang and Zhu, 2016 ). As a potential molecule with the activities of anti-inflammation (i.e., p38 MAPK signaling pathway) ( Kadam et al, 2007 ), anti-tubercular (i.e., tuberculosis) ( Nayak et al, 2018 ; Kumar et al, 2019 ), anti-chagas ( Marinho et al, 2021 ) and anti-virus (i.e., SARS-CoV-2) ( Ghosh et al, 2020 ; Lokhande et al, 2020 ), AMF is virtually screened through molecular docking and molecular dynamics simulation of in silico approaches in recent researches ( Table 4 ).…”

“…Cruzain has a catalytic site locating at the intersection of two domains, namely α -helices and β -Sheets, in which the residues are prominent. The molecular docking analysis shows that AMF has an interactive affinity simulations (-8.0 kcal/mol) with the catalytic site of cruzain ( Marinho et al, 2021 ). The interactions between AMF and cruzain are identified.…”

“…The interactions between AMF and cruzain are identified. They are three hydrogen bonds with the residues Gly20, Met68 and Ser64, a van der Waals with His162, an Amide-Pi with the Asp161, a Pi-Alkyl with Ala138, and a π - π stacking with Trp184 ( Marinho et al, 2021 ).…”

Quantum mechanical, molecular docking, molecular dynamics, ADMET and antiproliferative activity onTrypanosoma cruzi(Y strain) of chalcone (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(3-nitrophenyl)prop-2-en-1-one derived from a natural product

“…The Nosé–Hoover thermostat 51 was used to fix the system temperature (310 K) in all production simulations, while the system pressure was controlled using a Parrinello–Rahman barostat 52 in the NPT simulations. The geometry of the systems was minimized by the steepest descent algorithm 53 for 10 000 steps with a tolerance of 10 kJ mol −1 nm −1 followed by a conjugate gradient algorithm 54 for 10 000 steps with tolerance of 10 kJ mol −1 nm −1 .…”

Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach

“…Molecular docking and molecular dynamics simulation help in predicting the binding affinity and the stability of ligands in the binding pocket of target receptors [ 22 ]. Density functional theory is a computational method that is useful in predicting the pharmacological potentials and electronic properties of hit molecules in the treatment of diseases [ 23 ].…”