New arylated benzo[h]quinolines induce anti-cancer activity by oxidative stress-mediated DNA damage

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Pharmacology

Background:

• Benzo[h]quinolines are a class of heterocyclic compounds with potential biological activities.
• Developing novel anti-cancer agents is crucial for combating cancer globally.

Purpose of the Study:

• To evaluate the anti-cancer activity of benzo[h]quinolines against human cancer cell lines.
• To elucidate the mechanism of action of these compounds, focusing on DNA damage and apoptosis.

Main Methods:

• Cytotoxicity was assessed using the MTT assay on G361, H460, MCF7, and HCT116 cell lines.
• DNA oxidation, apoptosis-related gene expression, and cyclin-dependent kinases-2 (CDK2) activity were analyzed.
• Molecular docking was employed to predict interactions with target proteins like aromatase and CDK2.

Main Results:

• Compounds 3e, 3f, 3h, and 3j exhibited significant cytotoxicity against the tested cancer cell lines.
• Benzo[h]quinolines were found to induce oxidative stress-mediated DNA damage.
• Molecular docking confirmed favorable interactions with aromatase and CDK2, with acceptable predicted drug-likeness.

Conclusions:

• Benzo[h]quinolines possess promising anti-cancer activity mediated by DNA damage induction.
• These compounds represent potential leads for developing new cancer therapeutics.
• Further optimization is needed to enhance bioavailability and drug-likeness for clinical applications.