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

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Hari Narayana H N Moorthy (Author) Other; Vijayakumari Pratheepa (Author) Other; Maria J Ramos (Author) FCUP; Vitor Vasconcelos (Author) FCUP; Pedro A Fernandes (Author) FCUP

Journal

Title: Current Drug Targets

Vol. 15

Pages: 681-688

ISSN: 1389-4501

Publisher: Bentham Science

Indexing

ISI Web of Knowledge - 11 Citations

Scopus - 14 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-009-KY5

DOI: 10.2174/1389450115666140205152007

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8