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

• Published in: European journal of medicinal chemistry 2015-01, Vol.90, p.568-576
• Main Authors: Mahran, Asma M., Ragab, Sherif Sh, Hashem, Ahmed I., Ali, Mamdouh M., Nada, Afaf A.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative; Azo; Cell Proliferation - drug effects; Cisplatin - pharmacology; Diazepine; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HCT116 Cells; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - chemistry; Heterocyclic Compounds - pharmacology; Humans; Imidazole; Molecular Structure; Phenazine; 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; Pyrazine; Structure-Activity Relationship; Tumor Cells, Cultured
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.12.007

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. Novel series of phenazine derivatives were synthesized and evaluated as inhibitors of the proliferation of lung carcinoma (A549) and colorectal cancer (HCT116) cell lines through inhibition of human TRK activity. [Display omitted] •Novel heterocyclic compounds derived from 2,3-diaminophenazine were synthesized.•All compounds were characterized based on microanalytical and spectral data.•The compounds were screened for their antitumor activity against A549 and HCT116.•Five compounds were mostly antiproliferative agents as potent as the Cisplatin.•Compound 2 inhibited the TRK activity equal or more potent to the Cisplatin.