Molecular modelling, synthesis and antitumour activity of carbocyclic analogues of netropsin and distamycin - new carriers of alkylating elements

A series of netropsin and distamycin analogues was synthesised and investig ated by molecular modelling. The lowest-energy conformations of four carboc yclic lexitropsins, potential carriers of alkylating elements, were obtaine d using the HyperChem 4.0 program, and compared with the DNA-lexitropsin cr ystal structures from the Brookhaven National Laboratory Protein Data Bank. A method for synthesis of carbocyclic lexitropsins was elaborated, with th e use of a nitro group or azobenzene as precursors for the aromatic amino g roup. The influence of methoxy group in ortho position with respect to amid e groups on the activity of the new compounds was investigated. All of the compounds tested showed high antitumour activity in the standard cell line of mammalian tumour MCF-7.