Hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives and evaluation of their anticancer and antimycobacterial activity

Abstract

The design, synthesis, structure, and in vitro anticancer and antimycobacterial activity of new hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives are described. The strategy adopted for synthesis is straight and efficient, involving a three-step setup procedure: N-acylation, N-alkylation, and quaternization of nitrogen heterocycle. The solubility in microbiological medium and anticancer and antimycobacterial activity of a selection of new synthesized compounds were evaluated. The hybrid derivatives have an excellent solubility in microbiological medium, which make them promising from the pharmacological properties point of view. One of the hybrid compounds, 9 (with a benzimidazole and 8-aminoquinoline skeleton), exhibits a very good and selective antitumor activity against Renal Cancer A498 and Breast Cancer MDA-MB-468. Moreover, the anticancer assay suggests that the hybrid Imz (Bimz)/2-AP (8-AQ) compounds present a specific affinity to Renal Cancer A498. Concerning the antimycobacterial activity, only the hybrid compound, 9, has a significant activity. SAR correlations have been performed.

Keywords:

• Anticancer
• antimycobacterial
• hybrid imidazole (benzimidazole)/pyridine (quinoline)
• synthesis

Acknowledgements

The authors gratefully acknowledge the National Cancer Institute (Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, website: http://dtp.cancer.gov/) for the in vitro evaluation of anticancer activity and National Institutes of Health and the National Institute of Allergy and Infectious Diseases, Contract No. HHSN272201100009I, for the in vitro evaluation of anti-TB activity. We also thank the POSCCE-O 2.2.1, SMIS-CSNR 13984-901, No. 257/28.09.2010 Project, CERNESIM, for the NMR spectra.

Declaration of interest

The authors report no declarations of interest.

The authors are thankful to CNCSIS Bucuresti, Romania, grant PN-II-DE-PCE-2011-3-0038, no. 268/05.10.2011, for financial support.

Supplementary material available online