Pharmacochemical Studies of Synthesized Coumarin–Isoxazole–Pyridine Hybrids

Several new coumarin–isoxazole–pyridine hybrids were synthesized through a 1,3-dipolar cycloaddition reaction of nitrile oxides, prepared in situ from pyridine aldehyde oximes, with propargyloxy- or propargylaminocoumarins in moderate-to-good yields. Synthetic modifications were applied using (diace...

Full description

Saved in:
Bibliographic Details
Main Authors: Matina D. Douka, Ioanna M. Sigala, Catherine Gabriel, Eleni Nikolakaki, Dimitra J. Hadjipavlou-Litina, Konstantinos E. Litinas
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/30/7/1592
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Several new coumarin–isoxazole–pyridine hybrids were synthesized through a 1,3-dipolar cycloaddition reaction of nitrile oxides, prepared in situ from pyridine aldehyde oximes, with propargyloxy- or propargylaminocoumarins in moderate-to-good yields. Synthetic modifications were applied using (diacetoxyiodo)benzene (PIDA) at room temperature, microwave irradiation, or tert-butyl nitrite (TBN) under reflux. Coumarin, isoxazole, and pyridine groups were selected for hybridization in one molecule due to their biological impact to inhibit lipid peroxidation and an enzyme implicated in inflammation. Preliminary in vitro screening tests for lipoxygenase (LOX) inhibition and anti-lipid peroxidation for the new hybrids were performed. A discussion on the structure–activity relationship is presented. Compounds <b>12b</b> and <b>13a</b> were found to be potent LOX inhibitors with IC<sub>50</sub> 5 μΜ and 10 μΜ, respectively, while <b>12b</b> presented high (90.4%) anti-lipid peroxidation. Furthermore, hybrids <b>12b</b> and <b>13a</b> exhibited moderate-to-low anticancer activities on HeLa, HT-29, and H1437 cancer cells.
ISSN:1420-3049