Novel Pd(ii) pincer complexes bearing salicylaldimine-based benzothiazole derivatives: synthesis, structural characterization, DNA/BSA binding, and biological evaluation

Abstract

Novel Pd(II) pincer complexes (1–8) bearing the O,N,N-chelating ligand scaffold with different substituents on the phenyl ring (–H (HL¹), –Me (HL²), –OMe (HL³), –^tBu (HL⁴), –F (HL⁵), –Cl (HL⁶), –Br (HL⁷), and –I (HL⁸)) were synthesized and characterized by ¹H NMR, FT-IR, HRMS, and single crystal X-ray diffraction techniques. The molecular structures of complexes 1–3, and 5 demonstrated a distorted square planar geometry comprising two six-membered metallocyclic rings. According to the DNA/BSA binding study, which was performed using UV-visible and fluorescence spectroscopy techniques, the Schiff base ligands and their corresponding Pd(II) complexes possess strong binding affinity to DNA and BSA. The interaction between the complexes and the biomolecules was studied by molecular docking. Moreover, anticancer activities of the ligands and complexes against three human cancer cell lines (A549, HepG2, and T47D) were determined. The results indicate that complex 3 ([Pd(L³)Cl]) could significantly inhibit HepG2 cell proliferation and migration through the induction of apoptosis, intracellular ROS production, and S phase cell cycle arrest. Meanwhile, complex 5 ([Pd(L⁵)Cl]) showed the highest antiproliferative effect against T47D cancer cells with higher potency than cisplatin. Interestingly, both complexes 3 and 5 are less toxic to normal lung cells (IMR-90), as compared to the cancer cells, suggesting a promising model for novel anticancer drug development.