Abstract
The present research work describes the synthesis of new series of nicotinonitrile (2) and furo[2,3-b]pyridine (3) heterocycles bearing thiophene substituent. The nicotinonitrile derivatives were prepared from the corresponding 3-cyano-(2H)-pyridones (1a–f) in excellent yields. The ring cyclization of the nicotinonitrile derivatives (2a–f) in the presence of sodium methoxide provided the furo[2,3-b]pyridines (3a–f) in moderate to good yields. All the newly synthesized compounds were characterized by extensive NMR analysis data, including 1D-NMR experiments (1H and 13C) and 2D-NMR experiments (COSY, HMBC, HSQC), as well as HRESIMS data. All the final products were subjected for cytotoxic activity against five different tumour cell lines including HeLa (cervical), DU145 (prostate), HepG2 (liver), MDA-MB-231 (breast-ER negative) and MCF7 (breast-ER positive), in addition to HSF1184 (normal human fibroblast) using the MTT assay. Compounds 2d and 3e were found to exhibit promising cytotoxicity with IC50 of < 20 µM against all different tested tumour cell lines. In addition, these compounds showed high selectivity (40–287 folds) for tumour cells over normal cells.
Graphical abstract
Similar content being viewed by others
References
R.N. Kumar, Y. Poornachandra, P. Nagender, G. Mallareddy, N.R. Kumar, P. Ranjithreddy, C.G. Kumar, B. Narsaiah, Eur. J. Med. Chem. 108, 68 (2016)
J.M. Hung, H.G. Arabshahi, E. Leung, J. Reynisson, D. Barker, Eur. J. Med. Chem. 86, 420 (2014)
B.D. Dorsey, C. McDonough, S.L. McDaniel, R.B. Levin, C.L. Newton, J.M. Hoffman, P.L. Darke, J.A. Zugay-Murphy, E.A. Emini, W.A. Schleif, D.B. Olsen, M.W. Stahlhut, C.A. Rutkowski, L.C. Kuo, J.H. Lin, I.W. Chen, S.R. Michelson, M.K. Holloway, J.R. Huff, J.P. Vacca, J. Med. Chem. 43, 3386 (2000)
D. Barnes, R. Chopra, S.L. Cohen, J. Fu, M. Kato, P. Lu, M. Seepersaud, W. Zhang, Furopyridine compounds and uses thereof, Patent EP2560976A1 (2013)
C. Bathula, R. Mamidala, C. Thulluri, R. Agarwal, K.K. Jha, P. Munshi, U. Adepally, A. Singh, M.T. Chary, S. Sen, RSC Adv. 5, 90374 (2015)
N. Fokialakis, P. Magiatis, N. Aligiannis, S. Mitaku, F. Tillequin, T. Sévenet, Phytochemistry 57, 593 (2001)
S.N. Sirakanyan, A.A. Hovakimyan, A.S. Noravyan, Russ. Chem. Rev. 84, 441 (2015)
M.M. Ibrahim, Jordan J. Chem. 10, 98 (2015)
M. Al-Refai, M. Ibrahim, A. Al-Fawwaz, A. Geyer, Eur. J. Chem. 9, 375 (2018)
F. Denizot, R. Lang, J. Immunol. Methods 89, 271 (1986)
M.E. Nita, H. Nagawa, O. Tominaga, N. Tsuno, S. Fujii, S. Sasaki, C.-G. Fu, T. Takenoue, T. Tsuruo, T. Muto, Br. J. Cancer 78, 986 (1998)
D.B. Longley, D.P. Harkin, P.G. Johnston, Nat. Rev. Cancer 3, 330 (2003)
Acknowledgements
We are grateful to Al al-Bayt University (Mafraq, Jordan) for the financial support. We are also grateful to Universiti Sains Malaysia (Penang, Malaysia) for the kind financial support of the research stay of Dr. M. Ibrahim at school of chemical sciences and for the financial support for Dr. Azmi (Research Grant 304/PKimia/6313330) and Dr Abu Bakar (Research Grant 034/PTEKIND/6313329).
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Ibrahim, M.M., Al-Refai, M., Azmi, M.N. et al. Synthesis, characterization and cytotoxicity of new nicotinonitriles and their furo[2,3-b]pyridine derivatives. J IRAN CHEM SOC 16, 715–722 (2019). https://doi.org/10.1007/s13738-018-1549-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13738-018-1549-y