Synthesis and Biological Evaluation of Novel Hybrid Molecules Containing Purine, Coumarin and Isoxazoline or Isoxazole Moieties



Michael G. Kallitsakis1, Angelo Carotti2, Marco Catto2, Aikaterini Peperidou3, Dimitra J. Hadjipavlou-Litina3, Konstantinos E. Litinas1, *
1 Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
2 Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari “Aldo Moro”, V. Orabona 4, I-70125 Bari, Italy
3 Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece


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© 2017 Kallitsakis et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4. 0 International Public License (CC-BY 4. 0), a copy of which is available at: https://creativecommons. org/licenses/by/4. 0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this authors at the Laboratory of Organic Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece; Tel: +302310997864; Fax: +302310997679; E-mail: klitinas@chem.auth.gr


Abstract

Introduction:

The 1,3-dipolar cycloaddition reactions of nitrile oxides formed in situ (in the presence of NCS and Et3N) from the oximes of (purin-9-yl)acetaldehyde or (coumarinyloxy)acetaldehyde with allyloxycoumarins or 9-allylpurines, respectively resulted in 3,5-disubstituted isoxazolines. The similar reactions of propargyloxycoumarins or 9-propargylpurines led to 3,5-disubstituted isoxazoles by treatment with PIDA and catalytic amount of TFA.

Methods:

The new compounds were tested in vitro as antioxidant agents and inhibitors of soybean lipoxygenase LO, AChE and MAO-B.

Results:

The majority of the compounds showed significant hydroxyl radical scavenging activity. Compounds 4k and 4n presented LO inhibitory activity.

Conclusion:

Compound 13e presents an antioxidant significant profile combining anti-LO, anti-AChE and anti-MAO-B activities.

Keywords: Modified Homo-N-nucleosides, Purines, Coumarins, 1,3-dipolar Cycloaddition Reaction, Antioxidant activity, Anti-lipid peroxidation activity, Alzheimer’s Disease.