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

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 $ IC_{50} $ values of 0.03 mM and 0.02 mM, respectively; the $ IC_{50} $ 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. Graphical Abstract.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:32

Enthalten in:

Medicinal chemistry research - 32(2022), 2 vom: 24. Dez., Seite 239-253

Sprache:

Englisch

Beteiligte Personen:

Al-Mustafa, Ahmed [VerfasserIn]
Al-Zereini, Wael [VerfasserIn]
Ashram, Muhammad [VerfasserIn]
Al-Sha’er, Mahmoud A. [VerfasserIn]

Links:

Volltext [lizenzpflichtig]

Themen:

Acetylcholinesterase
Antibacterial
Antioxidant
Benzoxazepines
Cytotoxicity
Molecular docking

Anmerkungen:

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

doi:

10.1007/s00044-022-02999-4

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2133469559

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