Synthesis, structure, antimycobacterial and anticancer evaluation of new pyrrolo-phenanthroline derivatives

Abstract

A study concerning design, synthesis, structure and in vitro antimycobacterial and anticancer evaluation of new fused derivatives with pyrrolo[2,1-c][4,7]phenanthroline skeleton is described. The strategy adopted for synthesis involves a [3 + 2] dipolar cycloaddition of several in situ generated 4,7-phenanthrolin-4-ium ylides to different substituted alkynes and alkenes. Stereo- and regiochemistry of cycloaddition reactions were discussed. The structure of the new compounds was proven unambiguously, single-crystal X-ray diffraction studies including. The antimycobacterial and anticancer activity of a selection of new synthesized compounds was evaluated against Mycobacterium tuberculosis H37Rv under aerobic conditions and 60 human tumour cell line panel, respectively. Five of the tested compounds possess a moderate antimycobacterial activity, while two of the compounds have a significant antitumor activity against renal cancer and breast cancer.

• 3 + 2 Cycloadditions
• N-ylides
• pyrrolo[2,1-c][4,7]phenanthrolines

Acknowledgements

The authors gratefully acknowledge the National Institutes of Health and the National Institute of Allergy and Infectious Diseases (Contract No. HHSN272201100009I / HHSN27200001A08) for antimycobacterial tests and, to National Cancer Institute (NCI) for biological evaluation of compounds on their 60-cell panel: the testing was performed by the Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis (the URL to the Program's website: http://dtp.cancer.gov/). We also thank to the POSCCE-O 2.2.1, SMIS-CSNR 13984-901, Project no. 257/28.09.2010, CERNESIM, for the NMR experiments.

Declaration of interest

The authors report no conflict of interest. C. M. Al Matarneh is thankful for the financial support of grant POSDRU/159/1.5/S/137750, Project “Doctoral and Postdoctoral programs support for increased competitiveness in Exact Sciences research” co-financed by the European Social Found within the Sectorial Operational Program Human Resources Development 2007–2013.

Supplementary material available online

Supplemental Tables S1 and S2.