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Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)
Published on: January 20, 2016
Cytotoxicity and DNA binding property of phenanthrene imidazole with polyglycol side chains
Shuxiang Wang1, Hongdong Li, Chao Chen
1Chemical Biology Key Laboratory of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
Abstract:
A series of phenanthrene imidazole with polyglycol side chain (2a-2c and 3a-3c) were synthesized and characterized by IR, NMR and MS. The cytotoxicity of 2a-2c and 3a-3c against cancer cell lines (HL-60, BGC-823, Bel-7402 and KB) in vitro were measured using MTT method. The DNA binding properties of 3a-3c were investigated by UV, fluorescence, CD spectroscopies and thermal denaturation. The results indicate that 2a exhibits higher cytotoxicity than cisplatin against BGC-823 and Bel-7402 cell lines, 3b and 3c exhibit higher cytotoxicity than 2b and 2c against BGC-823, Bel-7402 and KB cell lines. The cytotoxic effect of 2a-2c decrease with the increase of side chains length, the cytotoxic effect of 3a-3c increased with the increasing length of side chains against BGC-823, Bel-7402 and KB cell lines. Compounds 3a-3c intercalated DNA with a vertical orientation in the intercalation pocket. The binding constants of 3a-3c with Ct-DNA are 1.68×10(6), 1.51×10(6) and 0.709×10(6)M(-1), respectively. The binding affinity of 3a-3c with Ct-DNA trended to decrease with the increasing length of polyglycol side chains.
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