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Synthesis and evaluation of new 2-oxo-1,2-dihydroquinoline-3-carboxamides as potent inhibitors against acetylcholinesterase enzyme

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Abstract

Alzheimer’s disease (AD), a worldwide mental disorder manifested with dementia symptoms, was used to be treated with tacrine. The latter use was terminated recently due to its hepatotoxicity. Thus, synthesis of tacrine analogues free of hepatotoxicity was attempted, a group of new 2-oxo-1,2-dihydroquinoline-3-carboxamides have been synthesized and properly characterized. Their biological evaluation in inhibiting acetylcholinesterase enzyme (AChE), was evaluated by the in-house gas chromatography method. The synthesized carboxamides showed a strong potency in inhibiting AChE. Nine compounds from the group had activities higher than or close to donepezil (the positive control, IC50 ca 10 nM). For example, compound 7 depicted IC50 of 7 nM and was subsequently evaluated by the in vivo zebra fish model. Interestingly compound 7 showed better recovery from scopolamine-induced dementia than that of donepezil. Further ex vivo and in vivo models have been established recently in the lab to evaluate the safety of these compounds.

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Acknowledgements

We wish to thank The University of Jordan represented by the Deanship of Academic Research for supporting and funding the project of (62/2019-2020).

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Authors and Affiliations

  1. Faculty of Pharmacy, The University of Jordan, Amman, Jordan

    Muhammed Alzweiri, Obada abu Saleh & Tamam Al-Helo

  2. Department of Chemistry, School of Science, The University of Jordan, Amman, Jordan

    Kamal Sweidan

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  1. Muhammed Alzweiri
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Correspondence to Muhammed Alzweiri.

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Alzweiri, M., Sweidan, K., Saleh, O.a. et al. Synthesis and evaluation of new 2-oxo-1,2-dihydroquinoline-3-carboxamides as potent inhibitors against acetylcholinesterase enzyme. Med Chem Res 31, 1448–1460 (2022). https://doi.org/10.1007/s00044-022-02922-x

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