Antiproliferative Evaluation of Novel 4-Imidazolidinone Derivatives as Anticancer Agent Which Triggers ROS-Dependent...

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Cancer Research

Background:

• Colorectal cancer (CRC) remains a leading cause of cancer mortality globally, necessitating the development of novel therapeutic agents.
• Existing treatments for CRC have limitations, driving the search for new chemotherapeutic molecules.

Purpose of the Study:

• To synthesize and evaluate novel imidazolidin-4-one derivatives for anticancer activity against CRC cell lines.
• To elucidate the molecular mechanism underlying the anticancer effects of the most potent compound, 9r.

Main Methods:

• Synthesis of a series of imidazolidin-4-one derivatives.
• Anticancer activity screening in various cancer cell lines, focusing on HCT116 and SW620 CRC cells.
• Investigation of apoptosis induction, reactive oxygen species (ROS) production, and the c-Jun N-terminal kinase (JNK) pathway.

Main Results:

• Compound 9r demonstrated significant anticancer activity in HCT116 and SW620 cells.
• Compound 9r induced apoptosis through the mitochondrial pathway by increasing ROS production.
• Elevated ROS activated the JNK pathway, further promoting apoptosis, an effect reversed by N-acetylcysteine (NAC).

Conclusions:

• Compound 9r, a novel imidazolidin-4-one derivative, exhibits potent anticancer effects against CRC cells.
• The mechanism involves ROS-mediated JNK activation and subsequent mitochondrial apoptosis.
• Compound 9r shows potential as a lead compound for future CRC therapeutic development.