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Current Drug Targets
ISSN (Print): 1389-4501
ISSN (Online): 1873-5592
Epub Abstract Ahead of Print
DOI: 10.2174/1389450115666140205152007      Price:  $95

Fused Aryl-Phenazines: Scaffold for the Development of Bioactive Molecules

Author(s): N.S. Hari Narayana Moorthy, V. Pratheepa, Maria J. Ramos, Vitor Vasconcelos and Pedro A. Fernandes
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Fused aryl phenazine derivatives especially benzo[a]phenazine, pyrido[a]phenazine, benzo[a]phenazine diones, tetrahydropyrido[a]phenazine (dermacozines), etc are important heterocyclic compounds exhibit various pharmacological activities, prominently in cancer cell lines. These compounds significantly intercalating with DNA and inhibit the activity of topoisomerase I and II enzymes (Topo I and II). XR11576, XR5944, NC-190 and NC-182 are belonging to this category, which are under clinical studies. Many fused aryl phenazine dione derivatives such as pyridazino[4,5-b]phenazine-5,12-diones, 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-diones, 6,11-dihydro-benzo[2,3-b]phenazine-6,11-diones, tetrahydropyrido[a]phenazine, etc have anticancer activity against various cancer cell lines. Benzo[a]phenazine diimine and other fused aryl phenazine compounds form coordination complex with the metal ions such as Ru, Rh, Zn and Pt that intercalate with the DNA and are used for the treatment of cancer. These molecules also possessed anticancer activity on MDR cancer cells and act as MDR modulating agents. The structure activity relationship of the fused aryl phenazine derivatives revealed that the presence of four or more nitrogen atoms in the compounds possessed better anticancer activity than molecules with less number of nitrogen atoms. Phenazine antibiotics derived from marine microbes are used for the treatment of microbial and worm diseases. Recent patent on these scaffolds showed that the benzo[a]phenazine derivatives possessed inhibitory activity on topoisomerase enzymes (Topo I and II), which act as anticancer agents and also used for the treatment of autoimmune disease and inflammatory conditions
REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, s/n, Rua do Campo Alegre, 4169-007 Porto, Portugal