Biological Appraisals of Cisplatin and Intercalating Analogies of Nanoscale Level Metal(II) Complexes

Abstract

A series of nanoscale-level metal complexes with bidentate (N2MCl[Formula: see text] and tetradentate (MN) chromophores have been employed as efficient cisplatin analogues and intercalating agents towards DNA and studied their anticancer activities against A549 cancer cells. Among them, complexes 1–6 exist with two labile chlorides similar to the chemotherapeutic inorganic drug cisplatin, which have been found to bind covalently with herring sperm DNA. Complexes 7–12 may undergo an intercalative mode of binding due to their structural differences relative to 1–6. The intrinsic binding constants obtained for complexes 7–12 were also significantly varied due to their structure and binding mode ([Formula: see text] and [Formula: see text] M[Formula: see text] for complexes, 1–3 and 4–6, respectively). However, complexes 7–9 have shown much stronger binding constants ([Formula: see text] M[Formula: see text]) due to their existing planarity which leads them to strong intercalation than their counterparts, 10–12 ([Formula: see text] M[Formula: see text]). The significantly higher binding constant values for complexes 1–3 may due to their planar structure and also may possibly lead to intercalation. Though all these complexes (1–12) have shown almost similar binding constants (1.26–2.0) in the electrochemical analysis, it implies that these complexes interact towards DNA with equal strength at their reduced oxidation (M[Formula: see text]) states. The obtained results in various spectral, electrochemical, relative viscosity changes, DNA cleavage studies revealed that these complexes 1–6 mimic the functional properties of cisplatin. Therefore, these nanostructured complexes could be substituted for cisplatin as a new family of non-platinum-based anticancer drugs in the future, after a sequence of in-vivo investigation. Their potential activity against A549 cancer cells has also been recorded using Hoechst staining and Propidium iodide images.