Targeting human telomeric and c-myc G-quadruplexes with alkynylplatinum(II) terpyridine complexes under molecular crowding conditions

Abstract

The interactions between alkynylplatinum(II) terpyridine complexes 1–3 and the G-quadruplex DNA, including c-myc and telomeric quadruplex DNA, are investigated both in dilute solution and under molecular crowding conditions. The UV–vis absorption spectroscopy, circular dichroism and molecular docking studies suggest that 1–3 associate with telomeric and c-myc G-quadruplexes via groove binding, and electrostatic interactions. Experimental studies indicate that under molecular crowding conditions (in the presence of 40wt% PEG 200), 1–2 show weak affinity for c-myc, while 3 still displays high affinity and selectivity for c-myc. On the other hand, 1–3 act as efficient and selective ligand for telomeric quadruplex DNA under molecular crowding conditions. The complex 3 exhibits excellent cytotoxicity against A549, K562 and SGC-7901, with IC50 values that are 35.0-fold, 10.0-fold, and 12.1-fold lower than the values of cisplatin under the same conditions, respectively.