Synthesis, characterization, DNA binding, topoisomerase I inhibition, and antiproliferation activities of (di-tert-butylbipyridine) platinum(II) complexes

Two mononuclear Pt(II) complexes, Pt(dbbpy)Cl2 (1) and [Pt(dbbpy)2](PF6)2 (2) (dbbpy = 4,4′-ditertbutyl-2,2′-biyridine) were synthesized and characterized by single-crystal X-ray diffraction analysis, elemental analysis, 1H NMR, and ESI–MS. Their binding affinities for both double-stranded (DS) calf thymus DNA (ct-DNA) and G-quadruplex DNA (HT21 and BCL-2) were investigated. In addition to structural differences, complex 1 displayed higher binding affinity for DS ct-DNA, whereas positively charged complex 2 was selective for binding to G-quadruplex DNA over DS DNA. The time-dependent cleavage of supercoiled circular plasmid pBR322 DNA by 1 was observed using agarose gel electrophoresis, whereas complex 2 hardly cleaved DS DNA. Stabilization of G-quadruplex HT21 DNA by both complexes was assessed by PCR stop assays. Both complexes exhibited moderate activities for inhibition of topoisomerase I as well as modest antiproliferation activities toward cancer cells in CKK-8 assays.