N-diphenylmethyl-2-propenamide: theoretical study of the structure and interaction with a DNA model system

N-diphenylmethyl-2-propenamide (NDP) was synthesised and characterised. Pha rmacological in vitro tests pointed out that NDP had a cytotoxic activity o n a human ovarian carcinoma comparable to that of doxorubicin. Hypothesisin g that this in vitro cytotoxic activity could be mainly due to intercalatin g interactions, between the drug and DNA fragments, ab initio calculations, at the Hartree-Fock (HF) level, were performed on the structure, and on th e conformational properties of NDP, whereas its interaction with an (AC)(TG ) dinucleotide triphosphate duplex (DD) was studied by the ONIOM method, at HF and PM3 level for NDP and DD, respectively. The supposed intercalation process with the DNA fragment was discussed in terms of the co-planarity of the aromatic rings present in the NDP molecule. (C) 2001 Elsevier Science B.V. All rights reserved.