The natural antibiotics, netropsin and distamycin, showed high selectivity of binding to the A-T rich regions of DNA, as well as both the antineoplastic and antiviral activity [1]. The model of binding of netropsin and distamycin with B-DNA became the inspiration to searches of compounds with similar DNA-ligand interaction.

New analogues of distamycin with modification of N-pyrrole rings were synthesized. In these investigations we concentrated on connecting benzene segments with some heterocyclic fragments. We chose three different aromatic diamines and four aromatic acid chlorides (Fig.1) and planned the synthesis of distamycin analogues.

Fig.1. Heterocyclic aromatic diamines (A, B, C) and aromatic acid chloride (1-4)

The free amine groups were acylated by acid chloride in stechiometry 1:2, to obtain twelve new compounds. All of them were investigated and showed antiproliferative and cytotoxic effects in the standard cell line of mammalian tumour MCF-7.

This work was founded by grant KBN No. 2P05F 017 27.

[1] Ch. Bailly, Sequence-specific recognition and modification of double-helical DNA by minor-groove binding conjugates structurally related to netropsin and distamycin, in: Advances in DNA Sequence-Specific Agents, 1998, 3, 97-156.

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