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

•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.

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.

Graphical abstractNovel 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.Figure optionsDownload full-size imageDownload as PowerPoint slide