Synthesis of new isoxazoline derivatives from harmine and evaluation of their anti-Alzheimer, anti-cancer and anti-inflammatory activities.

Abstract

In our study, a series of new harmine derivatives has been prepared by cycloaddition reaction using various arylnitrile oxides and evaluated in vitro against acetylcholinesterase and 5-lipoxygenase enzymes, MCF7 and HCT116 cancer cell lines. Some of these molecules have been shown to be potent inhibitors of acetylcholinesterase and MCF7 cell line. The greatest activity against acetylcholinesterase (IC50 = 10.4 µM) was obtained for harmine 1 and cytotoxic activities (IC50 = 0.2 µM) for compound 3a. Two derivatives 3e and 3f with the thiophene and furan systems, respectively, showed good activity against 5- lipoxygenase enzyme (IC50 = 29.2 and 55.5 µM, respectively).

• Authors: Insaf Filali, Jalloul Bouajila, Mansour Znati, Fatima Bousejra-El Garah, Hichem Ben Jannet
• Journal: Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 30 Issue 3 Pg. 371-6 (Jun 2015) ISSN: 1475-6374 [Electronic] England
• PMID: 25068731 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Antineoplastic Agents
• Cholinesterase Inhibitors
• Isoxazoles
• Lipoxygenase Inhibitors
• Harmine
• Arachidonate 5-Lipoxygenase
• Acetylcholinesterase

Topics

• Acetylcholinesterase (metabolism)
• Alzheimer Disease (drug therapy, enzymology, metabolism)
• Anti-Inflammatory Agents (chemical synthesis, chemistry, pharmacology)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Arachidonate 5-Lipoxygenase (metabolism)
• Cell Proliferation (drug effects)
• Cholinesterase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• HCT116 Cells
• Harmine (chemistry)
• Humans
• Inflammation (drug therapy)
• Isoxazoles (chemical synthesis, chemistry, pharmacology)
• Lipoxygenase Inhibitors (chemical synthesis, chemistry, pharmacology)
• MCF-7 Cells
• Molecular Structure
• Structure-Activity Relationship