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

The synthesis of three potentially tetradentate, N2S2 Schiff-base-ligands, containing a disulfide bond, (LSSLThio)-S-Thio(L1), (LSSLBr)-S-Br(L2) and (LSSLDiMeO)-S-DiMeO (L3) are reported. These ligands undergo reductive disulfide bond scission upon reaction with PPh3 in the presence of Zn2+ ion. [(LS)-S-DiOMe](-), [(LS)-S-Thio](-) and [(LS)-S-Br](-) are the resulting bidentate thiolate-imine anions respectively, which upon reaction with Zn2+ produce three new zinc (II) complexes: [Zn((LSN)-S-Thio)(2)] (1), [Zn((LSN)-S-Br)(2)] (2) and [Zn((LSN)-S-DiOMe)(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 (K-b = 2.2 x 10(4) to 1 x 10(5) 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 (k(q) = 1.66 to 3.4 x 10(13) L-1 mol 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.