Are Zn(II) pincer complexes efficient apoptosis inducers? a deep insight into their activity against A549 lung cancer
Athulya Das1, Muniyandi Sankaralingam1
1Bioinspired & Biomimetic Inorganic Chemistry Laboratory, Department of Chemistry, National Institute of Technology Calicut, Kozhikode-673601, Kerala, India. msankaralingam@nitc.ac.in.
Abstract:
To expand the array of chemotherapeutic drugs, earth-abundant metal complexes are found to be the future direction. In this regard, new zinc(II) complexes 1-3 of 8-aminoquinoline-based pincer ligands were synthesized, characterized and tested for their anticancer activity. The IC50 values of these complexes were estimated by an MTT assay to be 16.35-17.95 μM and 33.35-40 μM against A549 lung and MCF-7 breast cancer cells respectively. Among them, 3 was slightly better than the other complexes and, thus, subjected to detailed studies. Moreover, the ligand corresponding to 3 was less active against both the cell lines than the complex. Further, 3 showed no toxicity against normal fibroblast cell line L929, which instantly elevated the drug characteristic of our complex. An AO-EB staining assay revealed that 3 can induce apoptosis in A549, and it was quantified by flow cytometry as 22.77%. Moreover, the depolarization of the mitochondrial membrane potential determined by JC-1 staining indicated excess ROS production sites in the mitochondria, which was confirmed by carboxy-H2DCFDA staining. Interestingly, the present complexes show better activity than that of the standard drug cisplatin against A549 cells. Overall, the studies provided promising results that can be extended for clinical applications.
Insights
New zinc(II) complexes show potent anticancer activity against lung and breast cancer cells. These earth-abundant metal complexes induce apoptosis and exhibit lower toxicity than cisplatin, suggesting clinical potential.
Area of Science:
- Inorganic Chemistry
- Medicinal Chemistry
- Cancer Research
Background:
- The development of novel chemotherapeutic agents is crucial for cancer treatment.
- Earth-abundant metal complexes offer a promising alternative to traditional platinum-based drugs.
- 8-aminoquinoline-based pincer ligands provide a versatile scaffold for designing metal complexes.
Purpose of the Study:
- To synthesize and characterize novel zinc(II) complexes with 8-aminoquinoline-based pincer ligands.
- To evaluate the in vitro anticancer activity of these complexes against human lung (A549) and breast (MCF-7) cancer cell lines.
- To investigate the mechanism of action, including apoptosis induction and mitochondrial dysfunction.
Main Methods:
- Synthesis and characterization of zinc(II) complexes.
- MTT assay for cytotoxicity evaluation.
- Apoptosis assays (AO-EB staining, flow cytometry).
- Mitochondrial membrane potential and ROS detection (JC-1, carboxy-H2DCFDA staining).
Main Results:
- Zinc(II) complexes exhibited significant anticancer activity with IC50 values in the range of 16.35-40 μM.
- Complex 3 demonstrated superior efficacy and selectivity, with no observed toxicity in normal fibroblast cells (L929).
- Complex 3 induced apoptosis in A549 cells (22.77%) and caused mitochondrial dysfunction via ROS production.
- The synthesized complexes showed comparable or better activity than cisplatin against A549 cells.
Conclusions:
- Novel zinc(II) complexes based on 8-aminoquinoline pincer ligands possess significant anticancer properties.
- Complex 3 is a promising candidate for further development as a chemotherapeutic agent.
- These findings support the exploration of earth-abundant metal complexes for clinical cancer therapy.
