Convenient synthesis and antitumor evaluation of some new 9-ethyl-3-(hetaryl)carbazoles

Abstract

In continuing our efforts to develop new potent anticancer candidates, a new series of 9-ethylcarbazoles carrying at position 3 various heterocyclic substituents such as 2-imino-2H-chromenes 5a–e, 2-oxo-2H-chromenes 6a–e, 3-imino-3H-benzo[f]chromene 8, 3-oxo-3H-benzo[f]chromene 9, 2-pyridones 11, 14, pyrazole 19, pyrimidine 23, pyrido[1,2-a]pyrimidine 27, 2H-pyran-2-one 30, and pyrano[2,3-d]pyrimidinetrione 34 were efficiently synthesized, characterized and evaluated for their in vitro antitumor activity. The mechanism for the synthesis of compounds was also discussed. Most of the synthesized compounds were displayed the considerable anticancer activities against three human tumor cells lines, in particular, colon carcinoma (HCT-116), hepatocellular carcinoma (HepG-2) and breast cancer (MCF-7). Compound 6d proves as most active molecule in this study with special effectiveness against the human HCT-116 and HepG-2 as its IC₅₀ values are 1.50, 0.90 μM, respectively, when doxorubicin is compared. Compound 34 was also found to have high activity against HepG-2, HCT-116 and moderate activity against MCF-7.

Graphical Abstract

Keywords:

• Antitumor activity
• carbazole
• enaminonitrile
• 2H-chromen-2-one
• N-nucleophiles
• 2-pyridone

Acknowledgements

The authors extend their sincere appreciation to the King Abdulaziz City of Science and Technology (KACST) for supporting this work under grant agreement no 1-17-01-010-0005.

Additional information

Funding

This work was funded by the King Abdulaziz City of Science and Technology (KACST) under grant agreement no 1-17-01-010-0005.