Chromone-isoxazole hybrids molecules: synthesis, spectroscopic, MEDT, ELF, antibacterial, ADME-Tox, molecular docking and MD simulation investigations

Abstract

A mechanistic study was performed within the molecular electron density theory at the B3LYP/6-311G (d,p) computational level to explain the regioselectivity observed. An electron localization function analysis was also performed, and the results confirm the zwitterionic-type (zw-type) mechanism of the cycloaddition reactions between nitrile oxide and alkylated 4H-chromene-2-carboxylate derivatives and shed more light on the obtained regioselectivity experimentally. In silico studies on the pharmacokinetics, ADME and toxicity tests of the compounds were also performed, and it was projected that compounds 5a, 5b, 5c and 5d are pharmacokinetic and have favorable ADME profiles. Moreover, docking and molecular dynamics investigations were conducted to evaluate the interactions, orientation and conformation of the target compounds on the active sites of four distinct enzymes. The results of this investigation showed that two compounds, 5a and 5c, interacted effectively with the S. aureus active site while maintaining acceptable binding energy.

Communicated by Ramaswamy H. Sarma

Keywords:

• 1,3-Dipolar cycloaddition
• chromone-isoxazole
• regioselectivity
• MEDT
• ADME-Tox
• molecular docking
• molecular dynamics simulation

Authors' contributions

All the authors have contributed equally to the realization and the editing of this work. All the authors have given their agree to the publication of the manuscript.

Disclosure statement

The authors declare that there are no conflicts of interest related to this article.

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Funding

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