Biological studies and computational modeling of two new copper complexes derived from β-diketones and their nano-complexes

Abstract

The present study was conducted to design and develop new complexes and their metal-based nanodrug (registered as Casiopeínas^® for cancer) with a low toxicity, high efficiency, and high selectivity. First, complexes ([Cu(TTA)(bpy)₂] (1) and [Cu(TTA)₂(en)] (2) (TTA = 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione) were synthesized and characterized by X-ray diffraction studies, CHN analysis, conductivity measurements, FT-IR and UV-vis spectroscopy. Second, nanoparticles (NPs) of 3 and 4 with the average size of 63.04 and 85.39 nm were prepared with ultrasound. Scanning electron microscopy patterns of 3 and 4 showed irregular spherical and nanorod particles with spongy surface. Furthermore, the anticancer properties of compounds and nano-compounds were studied in MKN-45 cell line. Then, apoptosis studies were carried out utilizing AO/EB staining methods. Finally, to confirm the in vitro experimental data, the theoretical study was carried out by molecular docking studies. The results of DNA docking analysis revealed that 1 and 2 were inserted with DNA via the minor groove. The binding affinity monitors the order of 1 > 2, with a preference of binding to A-T over G-C base pairs sequences.

Keywords:

• Casiopeínas^®
• 2,2′-bipyridine
• β-diketone
• MTT assay
• apoptosis
• molecular docking studies
• intercalate

Acknowledgments

We thank Semnan University for supporting this study.