Current Medicinal Chemistry - Volume 9, Issue 18, 2002

Acridine derivatives are one of the oldest classes of bioactives, widely used as antibacterial and antiprotozoal agents. Some work in these areas continues, but recent research has focused mainly on their use as anticancer drugs, because of the ability of the acridine chromophore to intercalate DNA and inhibit topoisomerase enzymes.

Acridines have been used as chemotherapeutic agents against bacteria, protozoa and fungi, and they now find important use as anticancer drugs. There is a paucity of crystal structures of acridine-DNA complexes above the dinucleotide level, but recent structures of acridinecarboxamide topoisomerase II poisons complexed to hexanucleotides have allowed a molecular rationalization of their structure-activity relationships Read More

A series of potential topoisomerase II-mediated anticancer 9-anilinoacridine derivatives, which are designed to avoid bio-oxidation and possessed long duration of drug action, is reviewed. Among these agents, 3-(9-acridinylamino)-5- hydroxymethylaniline (AHMA) derivatives and their alkylcarbamates have been investigated and developed for potential clinical application.

Acronycine is active against a broad spectrum of solid tumors. Structure activity relationships demonstrated the crucial role of the 1,2-double bond. A hypothesis of bioactivation into 1,2-epoxide led to the development of a series of 1,2- dihydroxy-1,2-dihydroacronycine and 1,2-dihydroxy-1,2-dihydrobenzo[b]acronycine diesters that exhibited an increased potency when compared with the parent compound.

In the field of antitumor DNA-binding agents, the class of acridine derivatives play an important role either as number of compounds or as importance of their anticancer properties. We have synthesized a number of acridine derivatives as potential antitumor drugs, in which the chromophore is fully or partially constituted by acridine or by 9-acridone ring systems: from the pyrimido[5,6,1-de]acridines, to the pyri Read More