Fused aryl
phenazine derivatives (benzo[a]
phenazine, pyrido[a]
phenazine, benzo[a]
phenazine diones, tetrahydropyrido[a]
phenazine (dermacozines), etc) are important
heterocyclic compounds, which exhibit various pharmacological activities, prominently in
cancer cell lines. These compounds significantly intercalate between
DNA base pairs and inhibit the activities of
topoisomerase I and II
enzymes (
Topo I and II).
XR11576,
XR5944,
NC-190 and
NC-182 belong to
phenazine/fused aryl
phenazine category and are under clinical studies. Several fused aryl
phenazine dione compounds such as pyridazino[4,5-b]
phenazine-5,12-diones, 6,11-dihydro-pyrido[2,3-b]
phenazine-6,11-diones, 6,11-dihydrobenzo[2,3-b]
phenazine-6,11-diones, tetrahydropyrido[a]
phenazine, etc possessed anticancer activities on various
cancer cell lines. Benzo[a]
phenazine diimine and various other fused aryl
phenazine compounds form coordination complex with the
metal ions (Ru, Rh, Zn and Pt) that intercalate with the
DNA and are used for the treatment of
cancer. These molecules have influence on MDR
cancer cells and serve as
anticancer agents in MDR
cancer cells. The structure activity relationship of the fused aryl
phenazine derivatives revealed that the occurrence of four or more
nitrogen atoms in the compounds has better anticancer activity than those molecules with less number of
nitrogen atoms.
Phenazine antibiotics derived from marine microbes are used for the treatment of microbial and worm diseases. Recent patents on these scaffolds showed that the benzo[a]
phenazine derivatives have inhibitory activity on topoisomerase
enzymes (
Topo I and II) and that act as
anticancer agents.