Study of DNA Interactions with Steroidal and Nonsteroidal Estrogen–Platinum (II)–Based Anticancer Drugs

Abstract

The interactions of the steroidal and nonsteroidal estrogen–platinum (Pt) (II)–based anticancer drugs 16β-hydroxymethyl-16α-[8-(2-pyridin-2-yl-ethylamino)-3,6-dioxaoctyl]-1,3,5(10)-estratrien-3,17βdiol dichloroplatinum (II) (JPM-39), 4-[6-(2′-pyridylethylamino)-butyloxy)-phenyl]-7-methoxy-2,2-dimethyl-3-phenyl-chroman dichloroplatinum (II) (ATG-99), and 1-[(2-aminoethyl)amino]-9,10,10-tris(4-hydroxyphenyl)-9-decene dichloroplatinum (II) (GEB-28) with calf-thymus DNA in vitro using constant DNA concentration and various drug levels were studied. Fourier transform infrared (FTIR) and circular dichroism (CD) were studied with calf-thymus DNA in vitro using constant DNA concentration and various drug levels. FTIR, UV–visible, and CD spectroscopic methods were used to characterize the drug binding mode, the binding constant, and structural variations of DNA in aqueous solution. Spectroscopic evidence showed that the various Pt-based drugs bind indirectly to the major and minor grooves of DNA duplex with some degree of drug–phosphate interaction. The overall binding constants for JPM-39, GEB-28, and ATG-99 are K _JPM-39 = 4.2 (±0.75) × 10³ M⁻¹, K _GEB-28 = 3.4 (±0.65) × 10³ M⁻¹, and K _ATG-99 = 2.1 (±0.45) × 10³ M⁻¹. DNA aggregation occurs at high drug concentration, while DNA remains in the B-family structure.