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

Michael G Kallitsakis; Angelo Carotti; Marco Catto; Aikaterini Peperidou; Dimitra J Hadjipavlou-Litina; Konstantinos E Litinas

doi:10.2174/1874104501711010196

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

Open Med Chem J. 2017 Nov 30:11:196-211. doi: 10.2174/1874104501711010196. eCollection 2017.

Authors

Michael G Kallitsakis¹, Angelo Carotti², Marco Catto², Aikaterini Peperidou³, Dimitra J Hadjipavlou-Litina³, Konstantinos E Litinas¹

Affiliations

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.

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