Manganese(I) tricarbonyl complexes as potential anticancer agents.

Area of Science:

• Coordination Chemistry
• Medicinal Inorganic Chemistry
• Cancer Biology

Background:

• Development of novel metal-based anticancer agents is crucial for overcoming drug resistance.
• Manganese complexes offer potential as therapeutic agents due to their redox properties and lower toxicity compared to other metals.

Purpose of the Study:

• To synthesize and evaluate the antiproliferative activity of novel manganese(I) tricarbonyl complexes.
• To investigate the mechanism of action and in vivo toxicity of these complexes.

Main Methods:

• Synthesis of manganese complexes [Mn(CO)3(N^N)Br] (1, 3), [Mn(CO)3(acridine)(phendione)]OTf (2), and [Mn(CO)3(di-triazole)Br] (4).
• Antiproliferative assays using MTS against A2780, HCT116, HCT116doxR cancer cell lines, and human dermal fibroblasts.
• Analysis of reactive oxygen species (ROS) production, apoptosis, autophagy, and in vivo toxicity using CAM and zebrafish models.

Main Results:

• Complexes 1 and 2 demonstrated significant dose-dependent antiproliferative activity, with selectivity towards ovarian carcinoma cells (A2780) over fibroblasts.
• Exposure to complexes 1 and 2 induced ROS production, leading to apoptosis (intrinsic for 2, extrinsic for 1) and autophagy (for 1).
• Complexes did not target DNA or affect cell cycle progression but promoted cell migration and neovascularization (complex 2), with no observed in vivo toxicity.

Conclusions:

• Novel manganese complexes exhibit potent and selective anticancer activity, primarily through ROS-mediated apoptosis and autophagy.
• Complex 2's ability to potentiate cell migration and neovascularization suggests potential applications in early tumor stages and regenerative medicine.
• The low in vivo toxicity profile of these manganese complexes warrants further investigation as potential therapeutic agents.