Efficient Synthesis, Structural Characterization, Antibacterial Assessment, ADME-Tox Analysis, Molecular Docking and Molecular Dynamics Simulations of New Functionalized Isoxazoles
Aziz Arzine,
Hanine Hadni,
Khalid Boujdi,
Khalid Chebbac,
Najoua Barghady,
Yassine Rhazi,
Mohammed Chalkha,
Asmae Nakkabi,
Karim Chkirate,
Joel T. Mague,
Sarkar M. A. Kawsar,
Ghali Al Houari,
Mohammed M. Alanazi,
Mohamed El Yazidi
Affiliations
Aziz Arzine
Engineering Laboratory of Organometallic, Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, Sidi Mohamed Ben Abdellah University, P.O. Box 1796, Atlas, Fez 30000, Morocco
Hanine Hadni
LIMAS, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, P.O. Box 1796, Atlas, Fez 30000, Morocco
Khalid Boujdi
Faculty of Sciences and Technologies Mohammedia, University Hassan II, B.P. 146, Mohammedia 28800, Morocco
Khalid Chebbac
Laboratory of Biotechnology Conservation and Valorisation of Natural Resources, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdallah University, Fez 30000, Morocco
Najoua Barghady
Engineering Laboratory of Organometallic, Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, Sidi Mohamed Ben Abdellah University, P.O. Box 1796, Atlas, Fez 30000, Morocco
Yassine Rhazi
Engineering Laboratory of Organometallic, Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, Sidi Mohamed Ben Abdellah University, P.O. Box 1796, Atlas, Fez 30000, Morocco
Mohammed Chalkha
Engineering Laboratory of Organometallic, Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, Sidi Mohamed Ben Abdellah University, P.O. Box 1796, Atlas, Fez 30000, Morocco
Asmae Nakkabi
Engineering Laboratory of Organometallic, Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, Sidi Mohamed Ben Abdellah University, P.O. Box 1796, Atlas, Fez 30000, Morocco
Karim Chkirate
Laboratory of Heterocyclic Organic Chemistry URAC 21, Pharmacochemistry Competence Center, Av. Ibn Battouta, BP 1014, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10010, Morocco
Joel T. Mague
Department of Chemistry, Tulane University, New Orleans, LA 70118, USA
Sarkar M. A. Kawsar
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh
Ghali Al Houari
Engineering Laboratory of Organometallic, Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, Sidi Mohamed Ben Abdellah University, P.O. Box 1796, Atlas, Fez 30000, Morocco
Mohammed M. Alanazi
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Mohamed El Yazidi
Engineering Laboratory of Organometallic, Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, Sidi Mohamed Ben Abdellah University, P.O. Box 1796, Atlas, Fez 30000, Morocco
This work describes the synthesis, characterization, and in vitro and in silico evaluation of the biological activity of new functionalized isoxazole derivatives. The structures of all new compounds were analyzed by IR and NMR spectroscopy. The structures of 4c and 4f were further confirmed by single crystal X-ray and their compositions unambiguously determined by mass spectrometry (MS). The antibacterial effect of the isoxazoles was assessed in vitro against Escherichia coli, Bacillus subtilis, and Staphylococcusaureus bacterial strains. Isoxazole 4a showed significant activity against E. coli and B. subtilis compared to the reference antibiotic drugs while 4d and 4f also exhibited some antibacterial effects. The molecular docking results indicate that the synthesized compounds exhibit strong interactions with the target proteins. Specifically, 4a displayed a better affinity for E. coli, S. aureus, and B. subtilis in comparison to the reference drugs. The molecular dynamics simulations performed on 4a strongly support the stability of the ligand–receptor complex when interacting with the active sites of proteins from E. coli, S. aureus, and B. subtilis. Lastly, the results of the Absorption, Distribution, Metabolism, Excretion and Toxicity Analysis (ADME-Tox) reveal that the molecules have promising pharmacokinetic properties, suggesting favorable druglike properties and potential therapeutic agents.
