JOURNAL OF MOLECULAR STRUCTURE, vol.1256, 2022 (SCI-Expanded)
Novel biologically active N-Sugar-derived isoxazolidines derivatives (2a, 2b, 3a, 3b) have been synthesized diastereospecifically by 1,3-dipolar cycloaddition reaction of nitrones (a, b) with maleimide and maleic acid. Nitrones were prepared in a pure form as chiral open-chain sugar-derived nitrones in an effort to explore a new type of antimicrobial agents. FTIR, 1 H NMR, and 13 C NMR spectrometric analysis characterized the structures of the compounds. The synthesized compounds were examined for their antimicrobial activity using the disk diffusion method against Gram-negative bacteria Escherichia coli; the Gram-positive bacteria staphylococcus aureus and against pathogenic fungi Candida albicans and Microsporum gypseum. Isoxazolidines (3a, 2a, 3b) proved to have strong antimicrobial activity compared to the standard drugs, as well as Drug-likeness and pharmacokinetic characteristics were predicted. Pharmacokinetic studies indicated that most derivatives exhibit acceptable predictive ADME properties and excellent fit with the Lipinski rules. Molecular docking was used to examine the binding interactions of the most active analogues with the active site of the DNA gyrase enzyme (PDB id 1KZN). Results showed that the enhanced activity of compounds (3a, 3b, 2a) exhibited stronger docking scores binding to the active site than the Nitrofurazone (standard drug). These findings suggest that analogues (3a, 3b) can be used as the best candidates for designing and discovering novel antimicrobial agents. (c) 2022 Elsevier B.V. All rights reserved.