Antitumor Potential of Aza-bioisosterism in Anthracenedione-based Drugs

Aza-bioisosteres of anthracene-9,10-diones and of anthrapyrazoles comprise an innovative class of anticancer compounds. They are formally derived by introduction of one or more nitrogens into the carbocyclic ring system of the parent drugs. Bioisosteres exhibit extensive changes in the physico-chemical properties and in the interactions with the pharmacological targets, DNA and DNA-topoisomerase II, when compared to the carbocyclic analogues. A favourable spectrum of activity, reduced side effects and a unique tropism for solid tumors make the new derivatives a very interesting family of drugs. In particular, a 2-aza-anthracene-9,10-dione and a 9-aza-anthrapyrazole derivative are presently undergoing advanced clinical trials and appear to be promising in view of their approval as anticancer drugs.