Antitumor Activity and Mechanism Study of Riluzole and Its Derivatives

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Cancer Biology

Background:

• The search for effective and safe antitumor agents is ongoing.
• Riluzole derivatives offer a promising scaffold for developing new cancer therapies.

Purpose of the Study:

• To synthesize and evaluate novel riluzole alkyl derivatives for their antitumor potential.
• To assess the cytotoxicity and safety profile of these compounds against various cancer cell lines and normal cells.

Main Methods:

• Synthesis of riluzole alkyl derivatives (4a-4i).
• Cytotoxicity assessment using the CCK-8 assay against HeLa, HepG2, SP2/0, and MCF-7 cancer cell lines, and LO2 normal liver cells.
• Apoptosis and cell cycle analysis via flow cytometry.
• Cell migration assessment using wound healing assays.
• Protein expression analysis (Bcl-2, Bax) using Western blot.

Main Results:

• Most synthesized derivatives exhibited potent cytotoxic effects against tested cancer cell lines with low toxicity to normal LO2 cells.
• Compound 4a demonstrated significant anti-proliferative activity against HeLa cells (IC50 = 7.76 μmol/L) and was non-toxic to LO2 cells up to 65 μmol/L.
• Compound 4a induced early apoptosis and G2/M cell cycle arrest in HeLa cells, impaired cell migration, and modulated Bcl-2/Bax protein expression, increasing the Bax/Bcl-2 ratio.

Conclusions:

• Riluzole derivative 4a displays significant antitumor activity, particularly against cervical cancer (HeLa cells), by inducing apoptosis and cell cycle arrest.
• Compound 4a exhibits a favorable safety profile, with potent efficacy and low toxicity, making it a promising candidate for further investigation.