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9-Anilinoacridines as anticancer drugs

Valeriy A. Bacherikov

Abstract


The information about the structures, synthesis and biological activity of 9-anilinoacridines, highly active anticancer drugs studied in the last decade was reviewed. Structure – property relationships of the leading compounds 4’-(9-acridinylamino)-metansulfon-m-anisidine (m-AMSA) and 3-(9-acridinylamino)-5-hydroximethylaniline (AHMA), their mechanism of biological action aimed at inhibition of the ternary complex of DNA – Topoisomerase II – Drug and mechanisms of their degradation and excretion were considered. Among the new derivatives of 9-anilinoacridine the hybrids of AHMA and DNA minor groove binding agents, such as Distamycin A or Netropsin, were discussed. Hybrid molecules able to interact with the DNA by anilinoacridine residue and inhibit topoisomerase II, as well as conjugate to the minor groove of DNA, should show significant increasing of selectivity and proper high activity, and will also less contribute to drug resistance in cancer cells. Investigation of biological activity of 5-(9-acridinylamino)-o, m, p-toluidines and 5-(9-acridinylamino)-o, m, p-anisidines, which were synthesized in order to design of an anticancer agent molecule having high activity and low toxicity, was considered. The modification of the 9-anilinoacridine molecule by the variety of substituents and linkers, and the synthesis and cytotoxicity of hybrid compounds composed from 9-anilinoacridine molecule and nitrogen mustards attached to aniline and acridine residues were discussed in details.


Keywords


derivatives of 9-anilinoacridine; hybrid molecules; structure; antitumor activity; topoisomerase inhibitors; N-mustard alkylators

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DOI: http://dx.doi.org/10.15421/081416

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