Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti-Alzheimer, Anti-inflammatory, and Anticancer Activities

Title:Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti-Alzheimer, Anti-inflammatory, and Anticancer Activities

Volume: 12 Issue: 2

Author(s): Insaf Filali, Anis Romdhane, Mansour Znati, Hichem B. Jannet and Jalloul Bouajila

Affiliation:

Keywords: Peganum harmala, harmine, isoxazoles, anti-inflammatory, anti-xanthine oxidase, anticancer.

Abstract: Harmine 1 was extracted from the seeds of Peganum harmala. From this natural molecule, a new series of isoxazole derivatives with complete regiospecificity were prepared using 1,3-dipolar cycloaddition reactions with various arylnitrile oxides. Harmine and its derivatives were characterized by ¹H NMR, ¹³C NMR and HRMS. The evaluation of their anti-acetylcholinesterase (AChE), anti-5-lipoxygenase (5-LOX), anti-xanthine oxidase (XOD) and anticancer activities were studied in vitro against AChE, 5-LOX and XOD enzymes, respectively, and in HTC-116, MCF7 and OVCAR-3 cancer cell lines. The prepared derivatives were shown to be inactive against the XOD enzyme (0-38.3±1.9% at 100 M). Compound 2 exhibited the best anti-AChE activity (IC₅₀=1.9±1.5 µM). Derivatives 3a, 3b and 3d had moderate cytotoxic activities (IC₅₀=5.0±0.3 µM (3a) and IC50=6.3±0.4 µM (3b) against HCT 116 cells, IC₅₀=5.0±1.0 µM (3d) against MCF7 cells).

Cite this article as:

Filali Insaf, Romdhane Anis, Znati Mansour, Jannet B. Hichem and Bouajila Jalloul, Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti-Alzheimer, Anti-inflammatory, and Anticancer Activities, Medicinal Chemistry 2016; 12 (2) . https://dx.doi.org/10.2174/157340641202160209104115