Enhanced synthesis of novel multisubstituted isoxazolidines as potential antimicrobial and antioxidant agents using zinc (II) catalyst, and in silico studies

• Published in: Journal of molecular structure Vol. 1292; p. 136146
• Main Authors: Al-Adhreai, Arwa, ALSaeedy, Mohammed, Alrabie, Ali, Al-horaibi, Sultan A., Al-Qadsy, Inas, Alezzy, Abdulmajeed A, AL-Odayni, Abdel-Basit, Saeed, Waseem Sharaf, Farooqui, Mazahar
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15-11-2023
• Subjects: 1,3-dipolar cycloaddition reaction; Antimicrobial and; Antioxidant activity; Docking study; Drug-likeness; Lewis acid catalyst; Multisubstituted isoxazolidines; Drug-likeness; Lewis acid catalyst; Multisubstituted isoxazolidines; Antioxidant activity; 1,3-dipolar cycloaddition reaction; Docking study; Antimicrobial and
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.136146

•A new series of multisubstituted isoxazolidines was successfully synthesized by 1,3-dipolar cycloaddition and Zinc chloride was utilized as a catalyst.•Antimicrobial activities of the synthesized compounds were evaluated against various types of bacteria and fungi species.•The compounds also showed good antioxidant activity by in vitro assay.•The synthesized compounds followed Lipinski's rule of five, making them suitable for oral drug development.•Molecular docking studies further supported the in vitro antibacterial evaluation.
In the effort of our endeavour to synthesize new heterocyclic bioactive agents, we succeed the synthesis of a new series of Multisubstituted isoxazolidines (3-(4- substituted)-5-(1H-imidazol-1-yl)-2-methyl-1,2-oxazolidine derivatives (3a–l) by 1,3-dipolar cycloaddition between chiral nitrone (1a–l) and 1-vinylimidazole. The spectral data was utilized to verify and elucidate the structures and mechanistic routes of all the products. By utilizing zinc chloride as a catalyst, the reaction rate was significantly enhanced, resulting in a reduction of the reaction time by over 100-fold. After the synthesis process, our objective was to examine the effectiveness of the synthesized compounds as antimicrobial agents against a range of bacterial and fungal species. The antimicrobial properties of the compounds were assessed using the macro double broth dilution method. with some exhibiting higher potency than established antibiotics and antifungals. Additionally, the compounds exhibited good antioxidant activity by in vitro assay, with 3c, 3g, and 3l showing higher activity than ascorbic acid. The study also evaluated the drug-likeness of the synthesized compounds and found that they followed Lipinski's rule of five, making them suitable for oral drug development. Molecular docking studies further supported the in vitro antibacterial evaluation The synthesized compounds demonstrated an excellent binding mode with the target 1QFG protein, some outperformed a standard drug.