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Published on: April 22, 2019
Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell
Yoshiaki Sugita1, Koichi Takao1, Yoshihiro Uesawa2
1Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
Abstract:
Since many anticancer drugs show severe adverse effects such as mucositis, peripheral neurotoxicity, and extravasation, it was crucial to explore new compounds with much reduced adverse effects. Comprehensive investigation with human malignant and nonmalignant cells demonstrated that derivatives of chromone, back-bone structure of flavonoid, showed much higher tumor specificity as compared with three major polyphenols in the natural kingdom, such as lignin-carbohydrate complex, tannin, and flavonoid. A total 291 newly synthesized compounds of 17 groups (consisting of 12 chromones, 2 esters, and 3 amides) gave a wide range of the intensity of tumor specificity, possibly reflecting the fitness for the optimal 3D structure and electric state. Among them, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (compound 22), which belongs to 3-styrylchromones, showed the highest tumor specificity. 22 induced subG1 and G2 + M cell population in human oral squamous cell carcinoma cell line, with much less keratinocyte toxicity as compared with doxorubicin and 5-FU. However, 12 active compounds selected did not necessarily induce apoptosis and mitotic arrest. This compound can be used as a lead compound to manufacture more active compound.
Insights
Researchers explored new anticancer compounds to reduce adverse effects. Chromone derivatives showed high tumor specificity, with compound 22 as a promising lead for developing safer cancer treatments.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Oncology
Background:
- Current anticancer drugs exhibit severe adverse effects, including mucositis, peripheral neurotoxicity, and extravasation.
- There is a critical need for novel anticancer compounds with significantly reduced toxicity.
- Flavonoid derivatives, specifically chromones, are investigated as potential alternatives.
Purpose of the Study:
- To synthesize and evaluate novel chromone derivatives for enhanced tumor specificity and reduced toxicity.
- To identify lead compounds for the development of safer and more effective anticancer therapeutics.
Main Methods:
- Synthesis of 291 novel compounds across 17 groups, including chromones, esters, and amides.
- Comprehensive testing on human malignant and nonmalignant cells to assess tumor specificity.
- Evaluation of the most promising compounds, including 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (compound 22), for their effects on cancer cell cycle and toxicity.
Main Results:
- Chromone derivatives demonstrated significantly higher tumor specificity compared to lignin-carbohydrate complex, tannin, and flavonoid.
- Compound 22, a 3-styrylchromone, exhibited the highest tumor specificity among all synthesized compounds.
- Compound 22 induced subG1 and G2+M cell cycle arrest in oral squamous cell carcinoma cells with lower keratinocyte toxicity than doxorubicin and 5-FU.
Conclusions:
- Chromone derivatives represent a promising class of compounds for developing anticancer agents with improved tumor specificity and reduced adverse effects.
- Compound 22 serves as a valuable lead compound for the synthesis of more potent and safer anticancer drugs.
- Further research is warranted to optimize the structure of compound 22 for enhanced therapeutic efficacy.
