Search for New Type of Anticancer Drugs with High Tumor Specificity and Less Keratinocyte Toxicity

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Oncology

Background:

• Current anticancer drugs for oral squamous cell carcinoma (OSCC) exhibit significant cytotoxicity in normal oral keratinocytes.
• Developing targeted therapies with reduced side effects is crucial for effective OSCC treatment.

Purpose of the Study:

• To review research on tumor specificity and keratinocyte toxicity of nine compound groups synthesized in the laboratory.
• To identify lead compounds for developing novel anticancer drugs with improved safety profiles.

Main Methods:

• Synthesis and evaluation of 133 compounds for anticancer activity.
• Assessment of tumor specificity and cytotoxicity against normal oral keratinocytes.
• Quantitative structure-activity relationship (QSAR) analysis to correlate chemical properties with efficacy.

Main Results:

• Two compounds, a 3-styrylchromone [3] and a 3-styryl-2H-chromene [4], exhibited the highest tumor specificity and lowest keratinocyte toxicity.
• Compound [3] induced apoptosis in OSCC cells, potentially via glycerophospholipid pathway modulation.
• QSAR analysis indicated that molecular size and lipophilicity are key descriptors for the tumor specificity of compounds [3] and [4].

Conclusions:

• Compounds [3] and [4] represent promising lead structures for developing new anticancer drugs against OSCC.
• Chemical modification of these compounds could further enhance efficacy and reduce toxicity.
• Targeted drug design based on structural features is a viable strategy for improving OSCC therapeutics.