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 investigated by molecular modelling. The lowest-energy conformations of four carbocyclic lexitropsins, potential carriers of alkylating elements, were obtained using the HyperChem 4.0 program, and compared with the DNA-lexitropsin crystal structures from the Brookhaven National Laboratory Protein Data Bank. A method for synthesis of carbocyclic lexitropsins was elaborated, with the use of a nitro group or azobenzene as precursors for the aromatic amino group. The influence of methoxy group in ortho position with respect to amide 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.
Bartulewic
D
D
Department of Organic Chemistry, Medical Academy of Białystok, Poland. dbartule@amb.ac.bialystok.pl
Markowska
A
A
Wołczyński
S
S
Dabrowska
M
M
Rózański
A
A
D000477:Alkylating Agents / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001483:Base Sequence; D018360:Crystallography, X-Ray; D004273:DNA, Neoplasm; D004214:Distamycins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D009429:Netropsin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004214:Distamycins; D009429:Netropsin; C030000:stallimycin