Moorthy N S Hari Narayana, Pratheepa Vijayakumari, Ramos Maria J, Vasconcelos Vitor, Fernandes Pedro A
REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, s/n, Rua do Campo Alegre, 4169-007 Porto, Portugal.
Curr Drug Targets. 2014;15(7):681-8. doi: 10.2174/1389450115666140205152007.
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.
稠合芳基吩嗪衍生物（苯并[a]吩嗪、吡啶并[a]吩嗪、苯并[a]吩嗪二酮、四氢吡啶并[a]吩嗪（地马唑嗪等）是重要的杂环化合物，具有多种药理活性，在癌细胞系中尤为显著。这些化合物可显著插入DNA碱基对之间，并抑制拓扑异构酶I和II（拓扑异构酶I和II）的活性。XR11576、XR5944、NC - 190和NC - 182属于吩嗪/稠合芳基吩嗪类别，正在进行临床研究。几种稠合芳基吩嗪二酮化合物，如哒嗪并[4,5 - b]吩嗪 - 5,12 - 二酮、6,11 - 二氢吡啶并[2,3 - b]吩嗪 - 6,11 - 二酮、6,11 - 二氢苯并[2,3 - b]吩嗪 - 6,11 - 二酮、四氢吡啶并[a]吩嗪等，对多种癌细胞系具有抗癌活性。苯并[a]吩嗪二亚胺和各种其他稠合芳基吩嗪化合物与金属离子（钌、铑、锌和铂）形成配位络合物，该络合物可插入DNA中，用于癌症治疗。这些分子对多药耐药（MDR）癌细胞有影响，并在MDR癌细胞中用作抗癌剂。稠合芳基吩嗪衍生物的构效关系表明，化合物中存在四个或更多氮原子时比氮原子数较少的分子具有更好的抗癌活性。源自海洋微生物的吩嗪抗生素用于治疗微生物和蠕虫疾病。关于这些支架的近期专利表明，苯并[a]吩嗪衍生物对拓扑异构酶（拓扑异构酶I和II）具有抑制活性，并可作为抗癌剂。
