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Evaluation of antibacterial, antioxidant, cytotoxic, and acetylcholinesterase inhibition activities of novel [1,4] benzoxazepines fused to heterocyclic systems with a molecular modeling study

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Abstract

Microbial pathogenesis, cancer progression, and neurological diseases are associated with oxidative stress due to the increased production of reactive oxygen species (ROS). This work aims to evaluate the antioxidants, antibacterial, cytotoxic, and anti-cholinesterase activities of 1,4-benzoxazepines derivatives (Zepin 7–32), as well as in silico modeling of their mode of action. The cytotoxic activity of Zepin (7–32) measured against the MDA-MB-231 breast cancer cell line revealed that Zepin-16 and −25 were the most potent anti-breast cancer compounds with IC50 values of 0.03 mM and 0.02 mM, respectively; the IC50 values of other 1,4-benzoxazepines with anticancer activity were in the range of 0.05–0.32 mM. Zepin-15, −16, −17, −19, −20, −21, −22, and −25 compounds were the most potent antibacterial agents against at least one of the tested strains from both Gram-negative and Gram-positive bacterial strains by agar diffusion test. However, oxazino-1,4-benzoxazepines 14–19 and 25 were the only compounds that exhibited antioxidant activity in DPPH assay; their ability to scavenge the DPPH radicals was in the following order, Zepin-16>−18>−17>−14>−15>−25. Correlated with the antioxidant activity, 1,4-benzoxazepines derivatives at 50 μg/mL, caused inhibition in acetylcholinesterase (AChE) activity ranging from 9.5 to 81%. The % inhibition pattern of 1,4-benzoxazepine derivatives toward AChE was classified into high effects (≥50%), moderate effects (>30 to 50%) and low effects (<30%). Interestingly, in the current study, the exhibited biological activities of 1,4-benzoxazepine derivatives have been confirmed by molecular modeling studies.

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The data presented in this study are available on request from the corresponding author.

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Acknowledgements

The authors would like to thank Mutah University for its support and for providing space to perform the experiments. We are thankful to the Deanship of Scientific Research at Zarqa University for support through Biovia 2019 software.

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  1. Department of Biological Sciences, Mutah University, P.O. Box 7, 61710, Al-Karak, Jordan

    Ahmed Al-Mustafa & Wael Al-Zereini

  2. Department of Chemistry, Mutah University, P.O. Box 7, 61710, Al-Karak, Jordan

    Muhammad Ashram

  3. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Zarqa University, P.O. Box 132222, 13132, Zarqa, Jordan

    Mahmoud A. Al-Sha’er

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  1. Ahmed Al-Mustafa
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Al-Mustafa, A., Al-Zereini, W., Ashram, M. et al. Evaluation of antibacterial, antioxidant, cytotoxic, and acetylcholinesterase inhibition activities of novel [1,4] benzoxazepines fused to heterocyclic systems with a molecular modeling study. Med Chem Res 32, 239–253 (2023). https://doi.org/10.1007/s00044-022-02999-4

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