Cytotoxic platinum(ii) intercalators that incorporate 1R,2R-diaminocyclopentane

Abstract

Twelve metallointercalators of the type [Pt(I_L)(A_L)]²⁺, where A_L is either the R,R or S,S enantiomer of 1,2-diaminocyclopentane (DACP) and I_L is either 1,10-phenathroline, 4-methyl-1,10-phenanthroline, 5-methyl-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5,6-dimethyl-1,10-phenanthroline or 3,4,7,8-tetramethyl-1,10-phenanthroline, were synthesised, characterised and the cytotoxicity to the L1210 cell line was determined. The crystal structures of PHENRRDACP and PHENSS were obtained as monoclinic with a space group of P2₁ (a/Å = 11.4966, b/Å = 6.6983, c/Å = 12.0235) and P2₁ (a/Å = 11.5777, b/Å = 7.0009, c/Å = 12.5079), respectively. The R,R enantiomer of 1,2-diaminocyclopentane (RRDACP) produced the most cytotoxic metallointercalators. The most cytotoxic metallointercalators were 56MERRDACP and 47MERRDACP with IC₅₀ values of 0.16 and 0.17 μM, respectively, in comparison to cisplatin (1 μM).