DNA-BSA interaction, cytotoxicity and molecular docking of mononuclear zinc complexes with reductively cleaved N2S2 Schiff base ligands

Abstract

The synthesis of three potentially tetradentate, N2S2 Schiff-base-ligands, containing a disulfide bond, LThioSSLThio(L1), LBrSSLBr (L2) and LDiMeOSSLDiMeO (L3) are reported. These ligands undergo reductive disulfide bond scission upon reaction with PPh3 in the presence of Zn2+ ion. [LDiOMeS]−, [LThioS]− and [LBrS]− are the resulting bidentate thiolate-imine anions respectively, which upon reaction with Zn2+ produce three new zinc(II) complexes: [Zn(LThioSN)2] (1), [Zn(LBrSN)2] (2) and [Zn(LDiOMeSN)2] (3). The structures of (L1) and 1–3 complexes were determined by X-ray diffraction. The interaction of 1–3 with CT-DNA have been investigated by absorption, emission, and CD spectroscopic methods and thermal denaturation measurements. The resulting data reveal that 1–3 show effective binding to CT-DNA (Kb = 2.2 × 104 to 1 × 105 L mol−1). The binding mode of DNA with 1–3 has also been investigated by molecular docking. The protein binding ability of 1–3 has been tested by monitoring the tryptophan emission intensity using BSA as a model protein. The quenching mechanism of BSA by the zinc complexes is static (kq = 1.66 to 3.4 × 1013 L mol−1 s−1). It is remarkable that 1–3 exhibit effective cytotoxicity against two human tumour cell lines (HeLa and MCF-7). The potent cytotoxic effects of 2 and 3, with IC50 values of 19.93 and 20.11 respectively, are higher relative to clinically used cisplatin (IC50 = 23.50) against the MCF-7 cell line, indicating that 2 and 3 may have the potential to act as effective metal-based anticancer drugs.