Design, Synthesis, and Antiproliferative Activity of Benzopyran-4-One-Isoxazole Hybrid Compounds

Abstract

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a–d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC50 values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC50 values of 5a–d against normal HEK-293 cells were in the range of 102.4–293.2 μM. Compound 5a was screened for kinase inhibitory activity, proteolytic human serum stability, and apoptotic activity. The compound was found inactive towards different kinases, while it completely degraded after 2 h of incubation with human serum. At 5 μM concentration, it induced apoptosis in MDA-MB-231 by 50.8%. Overall, these findings suggest that new benzopyran-4-one-isoxazole hybrid compounds, particularly 5a–d, are selective anticancer agents, potentially safe for human cells, and could be synthesized at low cost. Additionally, Compound 5a exhibits potential anticancer activity mediated via inhibition of cancer cell proliferation and induction of apoptosis.

Tensile Overload Injures Human Alveolar Epithelial Cells through YAP/F-Actin/MAPK Signaling

“…The samples were then analyzed by flow cytometry. The percentage of apoptotic cells is the sum of the percentage of early and late apoptotic cells [20].…”

Alkaloid-Based Isoxazolylureas: Synthesis and Effect in Combination With Anticancer Drugs on the c6 Rat Glioma Model

“…The isoxazole ring is often used as a central core of compounds with anticancer effects acting as inhibitor of numerous targets including aromatase, tyrosine kinase, thymidylate, ER, PLA2, HDAC, HER2, HSP90 inhibition and apoptosis induction [5][6][7]. The structural features of isoxazole make it possible for multiple non-covalent interactions, especially hydrogen bonds (hydrogen bond acceptor N and O), - stacking (unsaturated five-membered ring) and hydrophilic interactions [8].…”