Molecular modelling of DNA-antitumour drug intercalation interactions: correlation of structural and energetic features with biological properties for a series of phenylquinoline-8-carboxamide compounds.

摘要: The crystal structure of the experimental antitumour compound N-(2-dimethylaminoethyl)-2-phenylquinoline-8-carboxamide has been determined. geometry and conformation have used as starting points for molecular modelling intercalative interactions with DNA shown by parent analogues phenyl ring located at alternative positions on quinoline chromophore. A mechanics force field program was energy minimization calculation intermolecular (enthalphic) binding energies. quinoline-8-carboxamide derivatives a substituent 4- or 5-position were judged to be poor intercalators in both structural energetic terms. By contrast, 2-, 3-, 6-phenyl all had high calculated energies groups involved stacking base pairs. order this series compounds found correlate well experimentally derived free vitro cytotoxic activity.