Novel palladium(II) complexes of dipodal bis(1,3,4-oxadiazole-5-thione) ligands: Syntheses, characterization, in vitro antiproliferative activity, DNA binding interactions, and theoretical insights

Abstract

The synthesis of two new palladium complexes of dipodal 2-mercapto-1,3,4-oxadiazole derivatives, [L1PdCl₂]₂ (C1, L1: 1,3-bis(5-thio-1,3,4-oxadiazol-2-yl)benzene, and [L2PdCl₂]₂ (C2, L2: 1,4-bis(5-thio-1,3,4-oxadiazol-2-yl)benzene have been reported. Both complexes were characterized by using a series of techniques including elemental analysis, ATR-IR, FAR-IR, ¹H and ¹³C NMR spectroscopy, ESI- and HR-MS spectrometry, UV–Vis spectroscopy, and XPS analysis. The in vitro biological anticancer activity of palladium(II) complexes and their related ligands against human breast cancer cell line (MCF-7) and the human breast normal cell line (MCF-10A) has been investigated. According to the antiproliferation assays, complexes C1 and C2 (IC₅₀ 75 ± 4 µМ and 88 ± 2 µМ, respectively) exhibited higher antitumor activity compared to their corresponding ligands (IC₅₀ values of 181 ± 15 µМ for L1 and 192 ± 11 µМ for L2). Both palladium(II) complexes exhibited low toxicity (≥180 μM) against the MCF-10A normal cell line. The cytotoxic efficiency of C1 was compared to that of the anticancer drug oxaliplatin. Density functional theory (DFT) calculations were performed to predict the chemical reactivity of the synthesized compounds. Furthermore, the mode of binding of L1, L2, C1 and C2 with DNA was investigated using electronic absorption monitoring, viscosity measurements, and molecular docking simulations. These investigations suggest that both ligands and complexes bind to DNA within the minor grooves. The results indicated that amide nitrogen, ether oxygen, thionic sulfur, and chlorine atoms as well as the aromatic rings of the ligands and their complexes are responsible for their groove binding and intercalation to DNA 1BNA and DNA 1Z3F conformations.