Synthesis, comprehensive characterization and investigation of biological properties of newly synthesized Pt(II)-aminothiazole complexes: Combining experimental and computational approach

Abstract

The synthesis of new platinum(II) complexes with 2-amino-6-methyl-benzothiazole and 2-amino-6-chlorobenzothiazole as ligands were reported and the proposed structure of the complexes were determined using elemental microanalysis, infrared, ¹H and ¹³C NMR spectroscopy. To verify the suggested structures a computational approach utilizing Density Functional Theory was implemented. The results showed a strong correlation with experimental data, confirming the hypothesized structures of investigated compounds.

The interactions of novel platinum(II) complexes with human serum albumin and calf thymus DNA were studied by fluorescence spectroscopy and UV-Vis absorption. The predominantly elevated values of the binding constant, K_b, and the Stern-Volmer quenching constant, K_SV, stem from the effective attachment of complexes to both HSA and CT-DNA. To establish the mode of interaction, viscosity measurements were conducted. The results showed that complexes are not performing intercalation between the DNA bases, and which probably bind to minor/major grooves.

In vitro cytotoxic effect of ligands and platinum(II) complexes was evaluated in the panel of cancer cell lines (mouse mammary carcinoma and colon cancer, and on human mammary carcinoma and colon cancer), and on non-tumor cells, mouse mesenchymal stem cell line using MTT assay. Platinum(II) complex with 2-amino-6-methyl-benzothiazole showed a very good cytotoxic activity mainly by inducing apoptosis.

In vitro antimicrobial assay of ligands and complexes was tested against 11 microorganisms using microdilution method and the minimum inhibitory concentration and minimum microbicidal concentration were identified. All tested compounds exhibited moderate antifungal activity and significantly better action on S. aureus ATCC 25,923.