Copyright (c) 2025 Hussein Ali Al-Bahrani, Shatha Abd Al-Jabbar, Hussein abd aljabbar Ismael, Zeyad Kadhim Oleiwi, Ammar Abdul-Hussein Awad, Abdul Amir H. Kadhum, Osama Hameed Rasheed, Zainab Hashim Ali
This work is licensed under a Creative Commons Attribution 4.0 International License.
Synthesis, Anticancer Evaluation and Molecular Docking of Novel Imidazo[1,2-a]pyridine Derivatives
Corresponding Author(s) : Hussein Ali Al-Bahrani
Asian Journal of Chemistry,
Vol. 37 No. 6 (2025): Vol 37 Issue 6, 2025
Abstract
Imidazo[1,2-a]pyridine and its derivatives are widely recognized for their antifungal and anti-yeast activities, primarily through ergosterol synthesis inhibition. In this study, an efficient and high-yield synthesis route is presented for three novel imidazo[1,2-a]pyridine derivatives based on 1-(4-phenoxyphenyl)ethan-1-one. These compounds were synthesized by reacting 1-(4-phenoxyphenyl)ethan-1-one with pyridin-2-amine in presence of iodine as a cyclizing agent and ethanol. The structures of the synthesized compounds (A, B and C) were confirmed by spectroscopic techniques, including FT-IR, 1H NMR and 13C NMR. The molecular docking studies were conducted to evaluate their binding affinity toward oxidoreductase, a key enzyme in breast cancer progression, Compound C exhibited the highest binding energy (-9.207 kcal/mol) and interacted with essential amino acids (His 222, Tyr 216, Lys 270), anticancer activity was assessed against MCF7 (breast cancer) and PC3 (prostate cancer) cell lines using the MTT assay. These findings suggest that structural optimization enhances selectivity toward breast cancer cells, This study highlights the potential of tailored imidazo[1,2-a]pyridine derivatives as targeted therapies, particularly for breast cancer, further mechanistic and in vivo investigations are warranted to validate their selectivity and safety profiles.
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- S. Samanta, S. Kumar, E.K. Aratikatla, S.R. Ghorpade and V. Singh, RSC Med. Chem., 14, 644 (2023); https://doi.org/10.1039/d3md00019b
- C. Enguehard-Gueiffier and A. Gueiffier, Mini Rev. Med. Chem., 7, 888 (2007); https://doi.org/10.2174/138955707781662645
- A.K. Bagdi, S. Santra, K. Monir and A. Hajra, Chem. Commun., 51, 1555 (2015); https://doi.org/10.1039/C4CC08495K
- A. Kumar, K. Pericherla, P. Kaswan and K. Pandey, Synthesis, 47, 887 (2015); https://doi.org/10.1055/s-0034-1380182
- M. Bamford, Prog. Med. Chem., 47, 75 (2009); https://doi.org/10.1016/S0079-6468(08)00203-8
- M. Dowsett, D. Smithers, J. Moore, P.F. Trunet, R.C. Coombes, T.J. Powles, R. Rubens and I.E. Smith, Eur. J. Cancer, 30, 1453 (1994); https://doi.org/10.1016/0959-8049(94)00281-9
- A.C. Humphries, E. Gancia, M.T. Gilligan, S. Goodacre, D. Hallett, K.J. Merchant and S.R. Thomas, Bioorg. Med. Chem. Lett., 16, 1518 (2006); https://doi.org/10.1016/j.bmcl.2005.12.037
- D. Davey, P.W. Erhardt, W.C. Lumma Jr., J. Wiggins, M. Sullivan, D. Pang and E. Cantor, J. Med. Chem., 30, 1337 (1987); https://doi.org/10.1021/jm00391a012
- A.N. Fajer, H.A. Al-Bahrani, A.A.H. Kadhum and M. Kazemi, Mol. Divers., 28, 3523 (2023); https://doi.org/10.1007/s11030-023-10751-2
- Y. Abe, H. Kayakiri, S. Satoh, T. Inoue, Y. Sawada, K. Imai, N. Inamura, M. Asano, C. Hatori, A. Katayama, T. Oku and H. Tanaka, J. Med. Chem., 41, 564 (1998); https://doi.org/10.1021/jm970591c
- W. An, W. Wang, T. Yu, Y. Zhang, Z. Miao, T. Meng and J. Shen, Eur. J. Med. Chem., 112, 367 (2016); https://doi.org/10.1016/j.ejmech.2016.02.004
- N. Nagarajan, G. Velmurugan, A. Prakash, N. Shakti, M. Katiyar, P. Venuvanalingam and R. Renganathan, Chem. Asian J., 9, 294 (2014); https://doi.org/10.1002/asia.201301061
- J.Y. Lee, J.Y. Shim, H.K. Kim, D. Ko, M.-H. Baik and E.J. Yoo, J. Org. Chem., 82, 4352 (2017); https://doi.org/10.1021/acs.joc.7b00358
- S. Ponnala, S.T.V.S. Kiran Kumar, B.A. Bhat and D. Prasad Sahu, Synth. Commun., 35, 901 (2005); https://doi.org/10.1081/SCC-200051674
- N. Denora, V. Laquintana, M.G. Pisu, R. Dore, L. Murru, A. Latrofa, G. Trapani and E. Sanna, J. Med. Chem., 51, 6876 (2008); https://doi.org/10.1021/jm8006728
- L. Albrecht, A. Albrecht, L.K. Ransborg and K.A. Jørgensen, Chem. Sci., 2, 1273 (2011); https://doi.org/10.1039/c1sc00122a
- K. Monir, A. Kumar Bagdi, S. Mishra, A. Majee and A. Hajra, Adv. Synth. Catal., 356, 1105 (2014); https://doi.org/10.1002/adsc.201300900
- C. He, J. Hao, H. Xu, Y. Mo, H. Liu, J. Han and A. Lei, Chem. Commun., 48, 11021 (2012); https://doi.org/10.1039/c2cc35927h
- H. Cao, X. Liu, J. Liao, J. Huang, H. Qiu, Q. Chen and Y. Chen, J. Org. Chem., 79, 11209 (2014); https://doi.org/10.1021/jo501671x
- H. Zhan, L. Zhao, J. Liao, N. Li, Q. Chen, S. Qiu and H. Cao, Adv. Synth. Catal., 357, 46 (2015); https://doi.org/10.1002/adsc.201400605
- S.K. Samanta and M.K. Bera, Org. Biomol. Chem., 17, 6441 (2019); https://doi.org/10.1039/C9OB00812H
- S. Santra, A.K. Bagdi, A. Majee and A. Hajra, Adv. Synth. Catal., 355, 1065 (2013); https://doi.org/10.1002/adsc.201201112
- W. Yu, X. Wang and L. Ma, Synthesis, 2445 (2011); https://doi.org/10.1055/s-0030-1260106
- N. Chernyak and V. Gevorgyan, Angew. Chem. Int. Ed., 49, 2743 (2010); https://doi.org/10.1002/anie.200907291
- A. Ganesher and G. Panda, Tetrahedron Lett., 60, 151317 (2019); https://doi.org/10.1016/j.tetlet.2019.151317
- Z. Chen, P. Liang, F. Xu, R. Qiu, Q. Tan, L. Long and M. Ye, J. Org. Chem., 84, 9369 (2019); https://doi.org/10.1021/acs.joc.9b01188
- Z.T. Bhutia, D. Das, A. Chatterjee and M. Banerjee, ACS Omega, 4, 4481 (2019); https://doi.org/10.1021/acsomega.8b03581
- N. Al-Lami and A.S. Mahmoud, Al-Nahrain J. Sci., 1, 26 (2018); https://doi.org/10.22401/ANJS.00.1.04
- A.A. Abdul-Hussein, O.H. Rasheed, D.H. Attol, M.T. Eesa, H.A. Al-Bahrani, Z.C. Hameed, A.A.H. Kadhum and S.A. Al-Jabbare, SSRN, (2025); https://doi.org/10.2139/ssrn.5129782
References
S. Samanta, S. Kumar, E.K. Aratikatla, S.R. Ghorpade and V. Singh, RSC Med. Chem., 14, 644 (2023); https://doi.org/10.1039/d3md00019b
C. Enguehard-Gueiffier and A. Gueiffier, Mini Rev. Med. Chem., 7, 888 (2007); https://doi.org/10.2174/138955707781662645
A.K. Bagdi, S. Santra, K. Monir and A. Hajra, Chem. Commun., 51, 1555 (2015); https://doi.org/10.1039/C4CC08495K
A. Kumar, K. Pericherla, P. Kaswan and K. Pandey, Synthesis, 47, 887 (2015); https://doi.org/10.1055/s-0034-1380182
M. Bamford, Prog. Med. Chem., 47, 75 (2009); https://doi.org/10.1016/S0079-6468(08)00203-8
M. Dowsett, D. Smithers, J. Moore, P.F. Trunet, R.C. Coombes, T.J. Powles, R. Rubens and I.E. Smith, Eur. J. Cancer, 30, 1453 (1994); https://doi.org/10.1016/0959-8049(94)00281-9
A.C. Humphries, E. Gancia, M.T. Gilligan, S. Goodacre, D. Hallett, K.J. Merchant and S.R. Thomas, Bioorg. Med. Chem. Lett., 16, 1518 (2006); https://doi.org/10.1016/j.bmcl.2005.12.037
D. Davey, P.W. Erhardt, W.C. Lumma Jr., J. Wiggins, M. Sullivan, D. Pang and E. Cantor, J. Med. Chem., 30, 1337 (1987); https://doi.org/10.1021/jm00391a012
A.N. Fajer, H.A. Al-Bahrani, A.A.H. Kadhum and M. Kazemi, Mol. Divers., 28, 3523 (2023); https://doi.org/10.1007/s11030-023-10751-2
Y. Abe, H. Kayakiri, S. Satoh, T. Inoue, Y. Sawada, K. Imai, N. Inamura, M. Asano, C. Hatori, A. Katayama, T. Oku and H. Tanaka, J. Med. Chem., 41, 564 (1998); https://doi.org/10.1021/jm970591c
W. An, W. Wang, T. Yu, Y. Zhang, Z. Miao, T. Meng and J. Shen, Eur. J. Med. Chem., 112, 367 (2016); https://doi.org/10.1016/j.ejmech.2016.02.004
N. Nagarajan, G. Velmurugan, A. Prakash, N. Shakti, M. Katiyar, P. Venuvanalingam and R. Renganathan, Chem. Asian J., 9, 294 (2014); https://doi.org/10.1002/asia.201301061
J.Y. Lee, J.Y. Shim, H.K. Kim, D. Ko, M.-H. Baik and E.J. Yoo, J. Org. Chem., 82, 4352 (2017); https://doi.org/10.1021/acs.joc.7b00358
S. Ponnala, S.T.V.S. Kiran Kumar, B.A. Bhat and D. Prasad Sahu, Synth. Commun., 35, 901 (2005); https://doi.org/10.1081/SCC-200051674
N. Denora, V. Laquintana, M.G. Pisu, R. Dore, L. Murru, A. Latrofa, G. Trapani and E. Sanna, J. Med. Chem., 51, 6876 (2008); https://doi.org/10.1021/jm8006728
L. Albrecht, A. Albrecht, L.K. Ransborg and K.A. Jørgensen, Chem. Sci., 2, 1273 (2011); https://doi.org/10.1039/c1sc00122a
K. Monir, A. Kumar Bagdi, S. Mishra, A. Majee and A. Hajra, Adv. Synth. Catal., 356, 1105 (2014); https://doi.org/10.1002/adsc.201300900
C. He, J. Hao, H. Xu, Y. Mo, H. Liu, J. Han and A. Lei, Chem. Commun., 48, 11021 (2012); https://doi.org/10.1039/c2cc35927h
H. Cao, X. Liu, J. Liao, J. Huang, H. Qiu, Q. Chen and Y. Chen, J. Org. Chem., 79, 11209 (2014); https://doi.org/10.1021/jo501671x
H. Zhan, L. Zhao, J. Liao, N. Li, Q. Chen, S. Qiu and H. Cao, Adv. Synth. Catal., 357, 46 (2015); https://doi.org/10.1002/adsc.201400605
S.K. Samanta and M.K. Bera, Org. Biomol. Chem., 17, 6441 (2019); https://doi.org/10.1039/C9OB00812H
S. Santra, A.K. Bagdi, A. Majee and A. Hajra, Adv. Synth. Catal., 355, 1065 (2013); https://doi.org/10.1002/adsc.201201112
W. Yu, X. Wang and L. Ma, Synthesis, 2445 (2011); https://doi.org/10.1055/s-0030-1260106
N. Chernyak and V. Gevorgyan, Angew. Chem. Int. Ed., 49, 2743 (2010); https://doi.org/10.1002/anie.200907291
A. Ganesher and G. Panda, Tetrahedron Lett., 60, 151317 (2019); https://doi.org/10.1016/j.tetlet.2019.151317
Z. Chen, P. Liang, F. Xu, R. Qiu, Q. Tan, L. Long and M. Ye, J. Org. Chem., 84, 9369 (2019); https://doi.org/10.1021/acs.joc.9b01188
Z.T. Bhutia, D. Das, A. Chatterjee and M. Banerjee, ACS Omega, 4, 4481 (2019); https://doi.org/10.1021/acsomega.8b03581
N. Al-Lami and A.S. Mahmoud, Al-Nahrain J. Sci., 1, 26 (2018); https://doi.org/10.22401/ANJS.00.1.04
A.A. Abdul-Hussein, O.H. Rasheed, D.H. Attol, M.T. Eesa, H.A. Al-Bahrani, Z.C. Hameed, A.A.H. Kadhum and S.A. Al-Jabbare, SSRN, (2025); https://doi.org/10.2139/ssrn.5129782
