Synthesis, Characterization, In Vitro and In Silico Investigation of Azo-Based Co(III), Zn(II), and Pd(II) Complexes Against Human Leukemia.

The new azo ligand (E)-2-((1H-indol-3-yl)diazenyl)benzoic acid (IDB) was synthesized and complexes of Co(III), Zn(II), and Pd(II) were prepared. Elemental analysis, FT‑IR, 1H‑NMR, 1 3C‑NMR, UV-vis, mass spectrometry, molar conductivity, magnetic susceptibility, XRD and FE-SEM were used to fully characterize the compounds. The spectroscopic data are consistent with the Co(III) and Zn(II) being coordinated as bidentate N,O-donors, with the azo nitrogen and deprotonated carboxylate oxygen, and with the Pd(II) being square-planar. The Pd(II) complex demonstrated cytotoxic activity against HL‑60 cells (IC50 = 134.4 µg/mL) with modest selectivity over normal HdFn fibroblasts (IC50 = 164.7 µg/mL, selectivity index = 1.23) among the tested complexes. Mechanistically, it significantly decreased malondialdehyde (MDA) levels in both cancer and normal cells, suggesting modulation of oxidative stress. The Pd(II) complex showed high binding affinity with Aurora kinase (Abl T315I mutant, PDB: 2V7A) with hydrogen bond with ASP 381 and ASN 322 and π-H interaction with LEU 248. The complexes are predicted to have reduced oral bioavailability, but are still good candidates for parenteral use, while the ligand is predicted to have good drug‑like properties. Overall, these results indicate that the Pd(II) complex is a promising lead compound for targeted leukemia therapy, but additional in vivo testing is needed.