Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors

Čadež, Tena; Grgičević, Ana; Ahmetović, Ramiza; Barić, Danijela; Hrvat, Nikolina Maček; Kovarik, Zrinka; Škorić, Irena

doi:10.3390/molecules25214872

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Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors

^1,†,

^2,†,

²,

^1,*

and

Irena Škorić

^2,*

Institute for Medical Research and Occupational Health, Ksaverska Cesta 2, 10000 Zagreb, Croatia

Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, 10000 Zagreb, Croatia

Division of Physical Chemistry, Rudjer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Academic Editor: Derek J. McPhee

Molecules 2020, 25(21), 4872; https://doi.org/10.3390/molecules25214872

Received: 6 October 2020 / Revised: 19 October 2020 / Accepted: 20 October 2020 / Published: 22 October 2020

(This article belongs to the Special Issue Enzymes Reacting with Organophosphorus Compounds)

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Abstract

A library of amine, oxime, ether, epoxy and acyl derivatives of the benzobicyclo[3.2.1]octene were synthesized and evaluated as inhibitors of both human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The majority of the tested compounds exhibited higher selectivity for BChE. Structural adjustment for AChE seems to have been achieved by acylation, and the furan ring opening of furo-benzobicyclo[3.2.1]octadiene results for compound 51 with the highest AChE affinity (IC₅₀ = 8.3 µM). Interestingly, its analogue, an oxime ether with a benzobicyclo[3.2.1]-skeleton, compound 32 was one of the most potent BChE inhibitors in this study (IC₅₀ = 31 µM), but not as potent as endo-43, an ether derivative of the benzobicyclo[3.2.1]octene with an additional phenyl substituent (IC₅₀ = 17 µM). Therefore, we identified several cholinesterase inhibitors with a potential for further development as potential drugs for the treatment of neurodegenerative diseases. View Full-Text

Keywords: acylation; benzobicyclo[3.2.1]octane/octene; benzylamines; cholinesterase; epoxidation; oximes

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MDPI and ACS Style

Čadež, T.; Grgičević, A.; Ahmetović, R.; Barić, D.; Hrvat, N.M.; Kovarik, Z.; Škorić, I. Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors. Molecules 2020, 25, 4872. https://doi.org/10.3390/molecules25214872

AMA Style

Čadež T, Grgičević A, Ahmetović R, Barić D, Hrvat NM, Kovarik Z, Škorić I. Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors. Molecules. 2020; 25(21):4872. https://doi.org/10.3390/molecules25214872

Chicago/Turabian Style

Čadež, Tena, Ana Grgičević, Ramiza Ahmetović, Danijela Barić, Nikolina M. Hrvat, Zrinka Kovarik, and Irena Škorić. 2020. "Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors" Molecules 25, no. 21: 4872. https://doi.org/10.3390/molecules25214872

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Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors

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