Palladium(II) complexes containing andrographolide appended N,O heterocyclic chelators: Investigation of anti-oxidant, anti-cancer and apoptotic activities

A series of new Pd(II) complexes were synthesized from the reaction of andrographolide appended hydrazide derivatives with potassium tetrachloropalladate K₂[PdCl₄]. The formation of the complexes was confirmed through structural assessments conducted using various spectroscopic techniques. From the spectral studies we confirmed that the ligands coordinated to Pd(II) ion via amine nitrogen and enone oxygen. The complexes were assessed for their antioxidant properties, demonstrating significant radical scavenging activity with a series of free radicals such as 1,1-diphenyl-2-picrylhydrazyl (DPPH^•), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid diammonium salt (ABTS^•+), Super oxide (O²⁻) and Nitric oxide (NO^•) radicals compared with standard antioxidants. Moreover, in vitro antiproliferative investigations conducted on A549 (human lung cancer) and HeLa (human cervical cancer) cell lines revealed significant cytotoxicity of the complexes, with lower IC₅₀ values compared to the standard metallo-drug cisplatin. Morphological alterations observed in HeLa and A549 cells when treated with IC₅₀ concentrations of the complexes, as examined through Acridine Orange-Ethidium Bromide (AO-EB) and 4′,6-diamidino-2-phenylindole (DAPI) staining techniques, indicated cell death via apoptosis. Biological studies indicated that AGC-Pd exhibited superior activity among others, further the percentages of the apoptotic and necrotic cells were determined by flow cytometric technique.