QSAR studies, docking and molecular dynamics simulation of a number of heterocyclic compounds including nitrogen oxide as new anti-tuberculosis agents

Subject Areas : applied chemistry

Ghasem Ghasemi ¹ (Assistant Professor, Department of Chemistry and Chemical Engineering, Rasht Branch, Islamic Azad University, Rasht, Iran)
Babak Motahary ² (PhD., Student, Department of Computer Engineering, Rasht Branch, Islamic Azad University, Rasht, Iran.)
Robabe SayadikordAbadi ³ (Assistant Professor, Department of Chemistry and Chemical Engineering, Rasht Branch, Islamic Azad University, Rasht, Iran)

Received: 2023-01-29 Accepted : 2023-04-06 Published : 2022-12-22

Keywords: QSAR, Tuberculosis,  N‑Oxide-Containing Heterocycles, Molecular dynamics simulation, Molecular docking,

Abstract :

Objectiv: Mycobacterium tuberculosis (Mtb), is agent of tuberculosis. A series of novel N‑Oxide-Containing Heterocycles have been reported as selective Mycobacterium tuberculosis inhibitors. QSAR, Docking, and Molecular Dynamics Simulation studies were investigated.Materials and Methods: Imperialist Competitive Algorithm (ICA), Partial least squares (PLS), Principle Component Regression (PCR), Least Absolute Shrinkage, Selection Operator (LASSO), and Monte-Carlo simulation were used to create QSAR models. The molecular docking and molecular dynamics simulation were carried out on Mycobacterium tuberculosis (Mtb) strain H37Rv (PDB: 4XGQ).Findings: Atomic masses, atomic sanderson electronegativities, Ghose–Viswanadhan-Wendoloski antiinfective-like index and Ghose –Viswanadhan-Wendoloski hyptonic-like index were important in our study. The SMILES files have been used with coralsea software. The root-mean square errors of the training set, and the test set for ICA model, were 0.2970, 0.1395 respectively. The results of the Monte-Carlo method were the following: n=7, R²=0.9931, Q²=0.9857, MAE=0.039 (Training set); n=6, R²=0.9413, Q²=0.9107, MAE=0.367 (Test set).Conclusion: Molecules 10 and 11 were presented as the most stable ones that may be introduced for further investigations, including clinical experiments.

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