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2000
Volume 10, Issue 1
  • ISSN: 2212-697X
  • E-ISSN: 2212-6988

Abstract

Background

Cyclooxygenase-2 (COX-2) is induced in response to proinflammatory conditions, and it is not only a key enzyme in the inflammatory process, but also seems to be highly expressed in various types of cancer cells. On the other hand, it is well documented that chemical compounds with spiro scaffolds in their structure could be effective chemical agents against cancer types.

Objective

In this study, the cytotoxicity effects of spiroisoxazoline derivatives containing a spiro-bridge of naphthalinone and chromanone were investigated.

Methods

The cytotoxicity effects of compounds - were evaluated by performing the MTT assay on the HT-29 (colorectal cancer), MCF-7 (breast cancer), and HEK-293 (normal kidney) cell lines. After that, a compound with high yield and remarkable cytotoxic activity was selected to analyze the cell cycle and apoptosis mechanism.

Results

The most effective cytotoxic activity was observed on HT-29 and MCF-7 cell lines of compounds (IC value: 1.07±0.28 µM) and (IC value: 11.92±1.07 µM). None of the compounds had a toxic effect on normal HEK-293 cells, except for compound with an IC value of 21.30±16.14 µM, whose effect was much lower than that of cisplatin and doxorubicin, known as anti-cancer agents. Subsequently, compound with significant yield and cytotoxic activity was investigated to evaluate cell cycle and apoptosis. The result showed that compound induced significant G0/G1 cell cycle arrest and apoptosis in HT-29 cells.

Conclusion

The selective COX-2 inhibitor compounds with spiroisoxazoline core structure could be suitable scaffolds for cytotoxic effects.

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2025-10-08

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/content/journals/ccand/10.2174/012212697X274833240408033609
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Anti-cancer Activity Evaluation of Naphthalenonic and Chromanonic Spiroisoxazoline Derivatives as Selective COX-2 Inhibitors on HT29 Cell Lines
Clinical Cancer Drugs 10, E110724231864 (2024); https://doi.org/10.2174/012212697X274833240408033609
/content/journals/ccand/10.2174/012212697X274833240408033609
/content/journals/ccand/10.2174/012212697X274833240408033609
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  • Article Type:     Research Article
Keyword(s): HEK-293; HT-29; MCF-7; MTT assay; selective COX-2 inhibitors; Spiroisoxazoline

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