Anticancer potential of Pd and Pt metallo-macrocycles of phosphines and 4,4΄-dipyridyldiselenide

Abstract

Reactions of [M(P∩P)(X)2] (M = Pd, Pt; X = NO3, OTf) and 4,4΄-dipyridyldiselenide yielded metallo-macrocyclic complexes [M(P∩P)(4,4΄-py2Se2)]n(X)2n capped by wide-bite-angle diphosphines (P∩P = dppf, Xantphos), which were characterized by NMR spectroscopy and ESI mass spectrometry. The X-ray analysis confirm the dimeric structure of [Pt(dppf)(4,4΄-py2Se2)]2(NO3)4 consisting of two Pt(II) centers bridged by 4,4΄-dipyridyldiselenides holding Pt-N bonds. In vitro cytotoxic activity of the complexes along with the previously synthesized [Pt(PEt3)2(4,4′-py2Se2)]n(OTf)2n was evaluated by MTT and clonogenic assay employing breast (MCF7), lung (A549), bone (U2OS) and ovarian (SKOV3) cancer cell lines. The results revealed the potent anticancer activity of these compounds. DNA damage was assessed by γ-H2AX, revealing that all the complexes induced DNA damage in the breast cancer cells. Further they also induced formation of micronuclei and other nuclear distortions. The complex [Pt(PEt3)2(4,4′-py2Se2)]n(OTf)2n has induced more nuclear abnormalities and exhibited higher anticancer activity than cisplatin.