7,8-Diacetoxy-3-(4-methylsulfonylphenyl)-4-phenylcoumarin Induces ROS-dependent Cell Death in the A549 Human Lung...

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Cancer Biology

Background:

• Coumarins are a large class of natural compounds with potential therapeutic applications.
• There is growing interest in synthesizing coumarin derivatives for disease treatment.

Purpose of the Study:

• To synthesize and evaluate the in-vitro cytotoxic activity of 3,4-Diarylcoumarins.
• To investigate the anticancer potential of these compounds in lung (A549) and prostate (PC-3) cancer cell lines.

Main Methods:

• Cytotoxic activity was assessed using crystal violet dye-binding.
• The most potent compound's effects on cell cycle, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and apoptosis were evaluated.

Main Results:

• Compound 4f (7,8-Diacetoxy-3-(4-(methylsulfonyl)phenyl)-4-phenylcoumrin) exhibited the highest cytotoxicity against A549 cells (CC50=13.5%±0.15μM).
• Compound 4f induced cell cycle arrest (G1/G0, S, G2), decreased MMP, increased ROS production, and triggered apoptosis.
• ROS-dependent cell death was confirmed by pretreatment with N-acetylcysteine (NAC).

Conclusions:

• The 3-methylsulfonyl and 7,8-diacetoxy groups are crucial for enhanced cytotoxic activity in 3,4-Diarylcoumarins.
• These findings suggest that 3,4-Diarylcoumarins can serve as a valuable template for developing novel lung cancer therapeutics.