Fluorine-Substituted Rhenium(I) Metallocycle: A New Class of Potent Anticancer Agent

Area of Science:

• Organometallic Chemistry
• Medicinal Chemistry
• Materials Science

Background:

• Rhenium(I) metallocycles are explored for therapeutic applications.
• Understanding the role of fluorine substitution in bioactivity is crucial.

Purpose of the Study:

• Synthesize and characterize novel fluorine- and nonfluorine-substituted rhenium(I) metallocycles.
• Evaluate their in vitro anticancer activity and biocompatibility.
• Investigate the mechanism of action for the most potent compound.

Main Methods:

• Coordination-driven one-pot solvothermal synthesis.
• Characterization using elemental analysis, mass spectrometry, IR, NMR, and PXRD.
• Single-crystal X-ray diffraction (SCXRD) for structural determination.
• In vitro cytotoxicity assays against HeLa and B16 cancer cells.
• Biocompatibility testing on L929 and C2C12 cell lines.
• Mechanism of action studies including ROS generation, mitochondrial membrane potential, DNA binding, and apoptosis induction.
• Molecular docking studies with B-DNA.

Main Results:

• Successful synthesis of two rhenium(I) metallocycles, C1 (fluorinated) and C2 (non-fluorinated).
• Both compounds demonstrated significant in vitro anticancer activity against cervical and skin cancer cells, exceeding that of cisplatin.
• The fluorine-substituted C1 exhibited superior anticancer efficacy compared to C2, indicating a notable fluorine effect.
• C1 induced intracellular ROS generation, disrupted mitochondrial membrane potential, bound to DNA, and triggered apoptosis in HeLa cells.
• Molecular docking revealed binding sites and interactions with B-DNA.

Conclusions:

• Fluorine substitution significantly enhances the anticancer potency of these rhenium(I) metallocycles.
• The metallocycles represent promising candidates for anticancer drug development.
• The observed activity is attributed to DNA damage and apoptosis induction.
• Further research into these compounds is warranted for therapeutic applications.