Fused Aryl-Phenazines: Scaffold for the Development of Bioactive Molecules
N.S. Hari Narayana Moorthy, Vijayakumari Pratheepa, Maria J. Ramos, Vitor Vasconcelos and Pedro A. Fernandes
Affiliation: REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, s/n, Rua do Campo Alegre, 4169-007 Porto, Portugal.
Keywords: Anticancer, benzo[a]phenazine, DNA intercalation, phenazine, topoisomerases.
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.
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