Mitochondria-localizing curcumin-cryptolepine Zn(II) complexes and their antitumor activity.

Area of Science:

• Coordination Chemistry
• Medicinal Chemistry
• Cancer Biology

Background:

• Metal complexes are promising mitochondrial-targeting agents for cancer therapy.
• Novel ligands like BPQA and PQA can be used to synthesize targeted metal complexes.
• Curcumin (H-Curc) possesses therapeutic properties and can be incorporated into metal complexes.

Purpose of the Study:

• To synthesize and characterize four novel zinc(II) complexes with potential anticancer activity.
• To investigate the mechanism of action of these complexes, particularly their mitochondrial targeting capabilities.
• To evaluate the in vitro and in vivo efficacy of the most promising complex as a therapeutic and imaging agent.

Main Methods:

• Synthesis and characterization of four Zn(II) complexes: [Zn(BPQA)Cl2] (Zn1), [Zn(BPQA)(Curc)]Cl (Zn2), [Zn(PQA)Cl2] (Zn3), and [Zn(PQA)(Curc)]Cl (Zn4).
• MTT assays to determine IC50 values against SK-OV-3/DDP and T-24 tumor cells, and cytotoxicity against HL-7702 normal cells.
• Fluorescence microscopy, Ca2+ and ROS level assays, mitochondrial membrane potential measurements, and in vivo tumor growth inhibition studies for probe Zn2.

Main Results:

• All four complexes (Zn1-Zn4) exhibited strong anticancer activities (IC50: 0.03-6.19 μM) against tested tumor cell lines.
• Complexes Zn1 and Zn2 showed low toxicity towards normal HL-7702 cells.
• Probe Zn2 demonstrated red fluorescence, accumulated in mitochondria, increased Ca2+ and ROS, reduced mitochondrial membrane potential, induced mitochondrial dysfunction, and inhibited T-24 tumor growth in vivo (50.7%).

Conclusions:

• The synthesized Zn(II) complexes possess significant anticancer properties.
• Probe Zn2 effectively targets mitochondria, leading to cancer cell death and tumor growth inhibition.
• Probe Zn2 holds promise for dual application in cancer therapy and as a mitochondrial imaging agent.