Synthesis, photophysical behavior and biomolecular reactivity of new triphenylphosphonium-based Pd(II)salphens as new anticancer candidates

Abstract

The synthesis of new bis-triphenylphosphonium-based dimethlysalphens (salphen = N,N`-bis-(salicylidene)-o-phenylenediimine) and their complexes (Pd(II)-salphens) for chemotherapeutic applications were reported. The in vitro anticancer efficacy of new compounds against human hepatocellular carcinoma (HepG2) cell lines demonstrated higher activity for Pd-complexes as compared with their parent ligands. Among tested compounds, Pd(II)-salphen3 was found to be the most potent one in the suppression of HepG2 proliferation (IC50 = 3.01 μM), ˜3-fold lower than the clinical drug (cisplatin, CDDP) (IC50 = 8.28 μM). The Pd(II)-salphens can effectively bind to CT-DNA via a non-covalent interaction (intercalation/ electrostatic) as revealed from the hyperchromism of 28–53% along with 3–6 nm bathochromism observed during the electronic absorption titration of Pd(II)-salphens with CT-DNA. On the other hand, the H-bonding and hydrophobic interactions play crucial roles in the binding of Pd(II)-salphens to BSA as indicating from the BSA fluorescence quenching by Pd(II) complexes. Noteworthy, Pd(II)-salphen3 displayed the highest reactivity towards DNA/ BSA with intrinsic binding constants (Kb/ KF) (3.01 × 105/ 2.95 × 106 M–1).