Synthesis and antiproliferative activity of novel polynuclear heterocyclic compounds derived from 2,3-diaminophenazine

Asma M Mahran; Sherif Sh Ragab; Ahmed I Hashem; Mamdouh M Ali; Afaf A Nada

doi:10.1016/j.ejmech.2013.12.007

Synthesis and antiproliferative activity of novel polynuclear heterocyclic compounds derived from 2,3-diaminophenazine

Eur J Med Chem. 2015 Jan 27:90:568-76. doi: 10.1016/j.ejmech.2013.12.007. Epub 2013 Dec 16.

Authors

Asma M Mahran¹, Sherif Sh Ragab², Ahmed I Hashem³, Mamdouh M Ali⁴, Afaf A Nada²

Affiliations

¹ Photochemistry Department, National Research Center, Dokki, Giza, Egypt. Electronic address: dr_asma_chem@yahoo.com.
² Photochemistry Department, National Research Center, Dokki, Giza, Egypt.
³ Department of Chemistry, Faculty of Science, Ain Shams University, Egypt.
⁴ Biochemistry Department, Division of Genetic Engineering and Biotechnology, National Research Centre, Dokki, Giza, Egypt.

PMID: 25497130
DOI: 10.1016/j.ejmech.2013.12.007

Abstract

2,3-Diaminophenazine 1 was used as a precursor for the preparation of some novel phenazine derivatives such as imidazo[4,5-b]phenazine-2-thione 2, its methylthio 3, ethyl 1-aryl-3H-[1,2,4]triazolo[2,3-a]imidazo[4,5-b]phenazines 8a-c, ethyl (2Z)-[3-aminophenazin-2-yl)amino](phenylhydrazono)ethanoate 9, pyrazino[2,3-b]phenazine derivatives 10, 12, 15-17, [1,4]diazepino[2,3-b]phenazine derivatives 13, 14, 2,3-dibenzoylaminophenazine 18, 1H-Imidazo[4,5-b]phenazine derivatives 20, 23a-c, 24, 25 and 4-[(E)-(3-amino phenazin-2-yl)diazenyl] derivatives 27-29. All compounds were tested as inhibitors of the proliferation of human lung carcinoma and colorectal cancer cell lines through inhibition of Tyrosine Kinases. Most of compounds exert good activity against the two cancer cell lines. Five compounds (1, 2, 3, 25 and 28) were found to possess the same activity as the standard drug Cisplatin.

Keywords: Antiproliferative; Azo; Diazepine; Imidazole; Phenazine; Pyrazine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects
Cisplatin / pharmacology
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
HCT116 Cells
Heterocyclic Compounds / chemical synthesis
Heterocyclic Compounds / chemistry
Heterocyclic Compounds / pharmacology*
Humans
Molecular Structure
Phenazines / chemical synthesis
Phenazines / chemistry
Phenazines / pharmacology*
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Protein-Tyrosine Kinases / antagonists & inhibitors*
Protein-Tyrosine Kinases / metabolism
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Antineoplastic Agents
Heterocyclic Compounds
Phenazines
Protein Kinase Inhibitors
2,3-diaminophenazine
Protein-Tyrosine Kinases
Cisplatin