Oxazinethione Derivatives as a Precursor to Pyrazolone and Pyrimidine Derivatives: Synthesis, Biological Activities, Molecular Modeling, ADME, and Molecular Dynamics Studies

Magda H Abdellattif; Mohd Shahbaaz; M M H Arief; Mostafa A Hussien

doi:10.3390/molecules26185482

Oxazinethione Derivatives as a Precursor to Pyrazolone and Pyrimidine Derivatives: Synthesis, Biological Activities, Molecular Modeling, ADME, and Molecular Dynamics Studies

Molecules. 2021 Sep 9;26(18):5482. doi: 10.3390/molecules26185482.

Authors

Magda H Abdellattif¹, Mohd Shahbaaz^{2

3}, M M H Arief⁴, Mostafa A Hussien^{5

6}

Affiliations

¹ Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
² South African Medical Research Council Bioinformatics Institute, University of Western Cape, Private Bag X17, Bellville, Cape Town 7535, South Africa.
³ Laboratory of Computational Modelling of Drugs, South Ural State University, 76 Lenin Prospects, 454080 Chelyabinsk, Russia.
⁴ Chemistry Department, Faculty of Science, Benha University, Benha 13511, Egypt.
⁵ Department of Chemistry, Faculty of Science, Port Said University, Port Said 42521, Egypt.
⁶ Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia.

Abstract

In this study, we used oxazinethione as a perfect precursor to synthesize new pyrimidine and pyrazole derivatives with potent biological activities. Biological activities were determined for all compounds against A. flavus, E. coli, S. aureus, and F. moniliform. Compounds 3, 4a-b, and 5 exhibited higher activities toward A. flavus, E. coli, S. aureus, and F. moniliform; this was indicated through the MIC (minimum inhibitory concentration). At the same time, anticancer activities were determined through four cell lines, Ovcar-3, Hela, MCF-7, and LCC-MMk. The results obtained indicated that compound 5 was the most potent compound for both cell lines. Molecular docking was studied by the MOE (molecular operating environment). The in silico ADME of compounds 2 and 5 showed good pharmacokinetic properties. The present research strengthens the applicability of these compounds as encouraging anticancer and antibacterial drugs. Moreover, JAGUAR module MD simulations were carried out at about 100 ns. In addition, spectroscopic studies were carried out to establish the reactions of the synthesized structure derivatives.

Keywords: ADME; molecular docking; one-pot synthesis; oxazines; pyrazole; pyrimidine.

MeSH terms

Anti-Infective Agents / chemical synthesis
Anti-Infective Agents / chemistry
Anti-Infective Agents / pharmacokinetics
Anti-Infective Agents / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacokinetics
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Escherichia coli / drug effects
Female
Humans
Microbial Sensitivity Tests
Molecular Docking Simulation
Molecular Dynamics Simulation
Molecular Structure
Oxazines / chemistry*
Pyrazolones / chemical synthesis*
Pyrimidines / chemical synthesis*
Pyrimidines / chemistry
Staphylococcus aureus / drug effects

Substances

Anti-Infective Agents
Antineoplastic Agents
Oxazines
Pyrazolones
Pyrimidines
pyrazolone