Sugar-boronate ester scaffold tethered pyridyl-imine palladium(ii) complexes: synthesis and their in vitro anticancer evaluation

Abstract

A series of five palladium(II) pyridyl-imine Schiff base complexes 5a–e containing boronate esters with protected sugar diols derived from D-xylose, L-sorbose and D-mannitol were designed and synthesized starting from pyridyl-imines generated in situ from 3-aminophenyl boronate ester of sugars 3a–e and 2-pyridinecarboxaldehyde, followed by the addition of Pd(cod)Cl₂ in dichloromethane solvent. All the complexes are remarkably stable orange/yellow crystalline solids and were obtained in good yields. The complexes were fully characterized by FT-IR, multinuclear NMR (¹H, ¹³C and ¹¹B), UV-visible spectroscopy, and elemental analysis. The solid state structures of 3a and 5a were established by single crystal X-ray diffraction analysis. The complexes have been tested for their in vitro anticancer activities against human colon cancer (HT-29) and breast cancer (MDA-MB-231) cell lines. All the complexes have shown moderate to good cytotoxicity in both the cancer cell lines with IC₅₀ values ranging from 4.27 to 34.76 μM. Strikingly, 5a displayed selective anticancer activity against both HT-29 and MDA-MB-231 cells with low IC₅₀ values 6.71 and 8.58 μM respectively. Results also demonstrate that some of these complexes are highly potent against HT-29 cells as compared to the other cancer cell lines. In particular, 1,2:5,6-di-O-isopropylidene-D-mannitol complex 5d showed a two-fold higher toxicity against HT-29 cells in comparison with that of cisplatin. In addition, these complexes are less toxic to model non-tumorigenic human embryonic kidney cells (HEK-293T). Furthermore, the interaction of the complexes with calf thymus DNA (CT-DNA) was investigated using spectroscopy and viscosity measurements. It was found that they intercalate with DNA.