Biological Activities Evaluation of Enantiopure Isoxazolidine Derivatives: In Vitro, In Vivo and In Silico Studies

Journal Article · Fri Mar 15 04:00:00 EDT 2019 · Applied Biochemistry and Biotechnology

DOI:https://doi.org/10.1007/S12010-018-2868-2· OSTI ID:22927817

Mosbah, Habib; Chahdoura, Hassiba ^[1]; Mannai, Asma; Snoussi, Mejdi ^[2]; Aouadi, Kaïss ^[3]; Abreu, Rui M. V. ^[4]; Bouslama, Ali ^[5]; Achour, Lotfi; Selmi, Boulbaba ^[1]

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1. University of Monastir, Laboratory of Bioresources, Integrative Biology and Valorization, Higher Institute of Biotechnology of Monastir (Tunisia)
2. University of Monastir, Laboratory of Genetic, Biodiversity and Valorization of Bioresources, Higher Institute of Biotechnology of Monastir (Tunisia)
3. University of Monastir, Laboratory of Heterocyclic Chemistry, Natural Products and Reactivity, Faculty of Sciences of Monastir (Tunisia)
4. Polytechnic Institute of Bragança, Mountain Research Center (CIMO), ESA (Portugal)
5. Sahloul University Hospital, Biochemistry Department, LR12SP11 (Tunisia)

A series of enantiopure isoxazolidines (3a–c) were synthesized by 1,3-dipolar cycloaddition between a (−)-menthone-derived nitrone and various terminal alkenes. The screened compounds were evaluated for their antioxidant activity by two in vitro antioxidant assays, including β-carotene/linoleic acid bleaching, and inhibition of lipid peroxidation (thiobarbituric acid reactive species, TBARS). The results revealed that compound 3b (EC{sub 50} = 0.55 ± 0.09 mM) was the most potent antioxidant as compared to the standard drug (EC{sub 50} = 2.73 ± 0.07 mM) using the TBARS assay. Furthermore, the antimicrobial activity was assessed using disc diffusion and microdilution methods. Among the synthesized compounds, 3c was found to be the most potent antimicrobial agent as compared to the standard drug. Subsequently, the acute toxicity study has also been carried out for the newly synthesized compounds and the experimental studies revealed that all compounds were safe up to 500 mg/kg and no death of animals were recorded. The cytotoxicity of these compounds was assessed by the MTT cell proliferation assay against the continuous human cell lines HeLa and compound 3c (GI{sub 50} = 46.2 ± 1.2 μM) appeared to be more active than compound 3a (GI{sub 50} = 200 ± 2.8 μM) and 3b (GI{sub 50} = 1400 ± 7.8 μM). Interestingly, all tested compounds displayed a good α-amylase inhibitory activity in competitive manner with IC{sub 50} values ranging between 23.7 and 64.35 μM when compared to the standard drug acarbose (IC{sub 50} = 282.12 μM). In addition, molecular docking studies were performed to understand the possible binding and the interaction of the most active compounds to the α-amylase pocket.

• OSTI ID: 22927817
• Journal Information: Applied Biochemistry and Biotechnology, Journal Name: Applied Biochemistry and Biotechnology Journal Issue: 3 Vol. 187; ISSN ABIBDL; ISSN 0273-2289
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALKENES
AMYLASE
ANTIMICROBIAL AGENTS
ANTIOXIDANTS
CAROTENOIDS
CELL PROLIFERATION
LINOLEIC ACID
TOXICITY