Copyright (c) 2026 Chandrashekhara Kumar B Chemistry, Raja Rajeshwari Surgical Oncology
This work is licensed under a Creative Commons Attribution 4.0 International License.
Synthesis and Molecular Docking Studies of Benzimidazole Hybrids Incorporating 1,3,4-Oxadiazole, 1,2,4-Triazole and Schiff Base as Potential Antibreast Cancer Agents
Corresponding Author(s) : B. Chandrashekhara Kumar
Asian Journal of Chemistry,
Vol. 38 No. 3 (2026): Vol 38 Issue 3, 2026
Abstract
A series of new benzimidazole-based hybrid compounds were synthesised by incorporating Schiff bases, 1,2,4-triazoles and 1,3,4-oxadiazoles and were evaluated for breast anticancer activity using molecular docking, MD simulations and ADME studies. The benzimidazole-based hybrid compounds were prepared through functionalisation of the benzimidazole scaffold via N-acylation, conversion to hydrazides and subsequent cyclisation to form 1,3,4-oxadiazoles and 1,2,4-triazoles. Molecular docking, MD simulations and ADME predictions were performed to assess anticancer potential particularly against breast-cancer-related targets. The oxadiazole hybrid (5e) showed moderate binding to β-tubulin suggesting the inhibition of microtubule function. Triazole derivatives (7a, 7b) exhibited high binding affinity to caspase-3 and PARP-1, which indicates pro-apoptotic and DNA repair inhibitory effects respectively. The Schiff base derivative (9a) demonstrated strong binding to ERα suggesting modulation of the hormone pathway. MD simulations demonstrated stable ligand-protein interactions and ADME analysis suggested good drug-likeness and oral absorption.
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- N. Xiong, H. Wu and Z. Yu, Front. Oncol., 14, 1405491 (2024); https://doi.org/10.3389/fonc.2024.1405491
- P. Pastena, H. Perera, A. Martinino, W. Kartsonis and F. Giovinazzo, Int. J. Mol. Sci., 25, 2559 (2024); https://doi.org/10.3390/ijms25052559
- D.K. Singh, H. Iqbal and M.A. Ansari, Curr. Org. Chem., 28, 733 (2024); https://doi.org/10.2174/0113852728303189240321084818
- K. Mahmood, Z. Akhter, F. Perveen, M. Bibi, H. Ismail, N. Tabassum, Aisha, S. Yousuf, A.R. Ashraf and M.A. Qayyum, RSC Adv., 13, 11982 (2023); https://doi.org/10.1039/D3RA00982C
- F. Vitali, L.D. Cohen, A. Demartini, A. Amato, V. Eterno, A. Zambelli and R. Bellazzi, PLoS One, 11, e0162407 (2016); https://doi.org/10.1371/journal.pone.0162407
- W.R. Mir, B.A. Bhat, A. Kumar, R. Dhiman, M. Alkhanani, M.Y. Dar, A. Almilaibary, S.A. Ganie and M.A. Mir, Front. Pharmacol., 14, 1135898 (2023); https://doi.org/10.3389/fphar.2023.1135898
- A. Kamal, A.B. Shaik, S. Polepalli, V. Santosh Reddy, G. Bharath Kumar, S. Gupta, K.V.S. Rama Krishna, A. Nagabhushana, R.K. Mishra and N. Jain, Org. Biomol. Chem., 12, 7993 (2014); https://doi.org/10.1039/C4OB01152J
- A. Vaidya, D. Pathak and K. Shah, Chem. Biol. Drug Des., 97, 572 (2021); https://doi.org/10.1111/cbdd.13795
- A.M. Abdelhakem and M.N. El-Shimaa, Octahedron Drug Res., 60, 112 (2024).
- N. Kulabaş, E. Tatar, Ö. B. Özakpınar, D. Özsavcı, C. Pannecouque, E. De Clercq, and İ. Küçükgüzel, Eur. J. Med. Chem., 121, 58 (2016); https://doi.org/10.1016/j.ejmech.2016.05.017
- T. Mondal, A.V.S. Lavanya, A. Mallick, T.L. Dadmala, R.M. Kumbhare, U. Bhadra and M.P. Bhadra, Apoptosis, 22, 786 (2017); https://doi.org/10.1007/s10495-017-1367-1
- Z.Q. Liao, C. Dong, K.E. Carlson, S. Srinivasan, J.C. Nwachukwu, R.W. Chesnut, A. Sharma, K.W. Nettles, J.A. Katzenellenbogen and H.B. Zhou, J. Med. Chem., 57, 3532 (2014); https://doi.org/10.1021/jm500268j
- B. Nabuurs, M. Wagener and J. de Vlieg, J. Med. Chem., 50, 6507 (2007); https://doi.org/10.1021/jm070593p
- G.M. Sastry, M. Adzhigirey, T. Day, R. Annabhimoju, W. Sherman, J. Comput. Aided Mol. Des., 27, 221 (2013).
- R.C. Johnston, K. Yao, Z. Kaplan, M. Chelliah, K. Leswing, S. Seekins, S. Watts, D. Calkins, J. Chief Elk, S.V. Jerome, M.P. Repasky and J.C. Shelley, J. Chem. Theory Comput., 19, 2380 (2023); https://doi.org/10.1021/acs.jctc.3c00044
- R.A. Friesner, J.L. Banks, R.B. Murphy, T.A. Halgren, J.J. Klicic, D.T. Mainz, M.P. Repasky, E.H. Knoll, M. Shelley, J.K. Perry, D.E. Shaw, P. Francis and P.S. Shenkin, J. Med. Chem., 47, 1739 (2004); https://doi.org/10.1021/jm0306430
- Z. Kaplan, S. Ehrlich and K. Leswing, Benchmark Study of DeepAuto-QSAR, ChemProp and DeepPurpose on the ADMET Subset of the Therapeutic Data Commons, Schrödinger, Inc. (2022); https://www.schrodinger.com/wpcontent/uploads/2023/10/22_086_machine_learning_white_paper_r4-1.pdf
- A.S. Shokouhi Asl, S. Ranjbar, M.H. Sayahi, Z. Dehghani, M. Emami, A.M. Taherkhani, M. Negahdaripour, N. Dastyafteh, S. Safapoor, A. Ghahramani, M.R. Mohajeri-Tehrani, B. Larijani, M. Mahdavi and Y. Ghasemi, RSC Adv., 15, 37447 (2025); https://doi.org/10.1039/D5RA02760H
- A.M. Malebari, M.A.M. Ali, A. Musa, M.E.A. Zaki, S.M. Gomha, M.A. Soliman, M.A. Abdelgawad, D.G.T. Parambi, M.R. Aouad, H.S. Abulkhair and H.E.A. Ahmed, RSC Adv., 15, 47601 (2025); https://doi.org/10.1039/D5RA07972A
- B. Huwaimel, A.S. Abouzied, M.E.A. Zaki, A. Alamri, B. Farag, S. Alqarni and S.M. Gomha, ChemistryOpen., 14, e202500288 (2025); https://doi.org/10.1002/open.202500288
- M.N. El-Bayaa, A.M. Srour, A.L. Alanzy, S. Messaoudi, A.A. Abd-Rabou, A. Saleh, M.G.A. Saleh and W.A. El-Sayed, Future Med. Chem., 17, 2927 (2025); https://doi.org/10.1080/17568919.2025.2587567
- A.M. Srour, M.N. El-Bayaa, A. Temirak, A.L. Alanzy, H.M. Awad, A. Saleh, M.G. Saleh and W.A. El-Sayed, Sci. Rep., 15, 25514 (2025); https://doi.org/10.1038/s41598-025-96675-3
- S. Alqahtani, M.A. Al-Omar, H.A. Ghabbour and A.A. El-Emam, Molecules., 28, 4123 (2023); https://doi.org/10.3390/molecules28104123
References
N. Xiong, H. Wu and Z. Yu, Front. Oncol., 14, 1405491 (2024); https://doi.org/10.3389/fonc.2024.1405491
P. Pastena, H. Perera, A. Martinino, W. Kartsonis and F. Giovinazzo, Int. J. Mol. Sci., 25, 2559 (2024); https://doi.org/10.3390/ijms25052559
D.K. Singh, H. Iqbal and M.A. Ansari, Curr. Org. Chem., 28, 733 (2024); https://doi.org/10.2174/0113852728303189240321084818
K. Mahmood, Z. Akhter, F. Perveen, M. Bibi, H. Ismail, N. Tabassum, Aisha, S. Yousuf, A.R. Ashraf and M.A. Qayyum, RSC Adv., 13, 11982 (2023); https://doi.org/10.1039/D3RA00982C
F. Vitali, L.D. Cohen, A. Demartini, A. Amato, V. Eterno, A. Zambelli and R. Bellazzi, PLoS One, 11, e0162407 (2016); https://doi.org/10.1371/journal.pone.0162407
W.R. Mir, B.A. Bhat, A. Kumar, R. Dhiman, M. Alkhanani, M.Y. Dar, A. Almilaibary, S.A. Ganie and M.A. Mir, Front. Pharmacol., 14, 1135898 (2023); https://doi.org/10.3389/fphar.2023.1135898
A. Kamal, A.B. Shaik, S. Polepalli, V. Santosh Reddy, G. Bharath Kumar, S. Gupta, K.V.S. Rama Krishna, A. Nagabhushana, R.K. Mishra and N. Jain, Org. Biomol. Chem., 12, 7993 (2014); https://doi.org/10.1039/C4OB01152J
A. Vaidya, D. Pathak and K. Shah, Chem. Biol. Drug Des., 97, 572 (2021); https://doi.org/10.1111/cbdd.13795
A.M. Abdelhakem and M.N. El-Shimaa, Octahedron Drug Res., 60, 112 (2024).
N. Kulabaş, E. Tatar, Ö. B. Özakpınar, D. Özsavcı, C. Pannecouque, E. De Clercq, and İ. Küçükgüzel, Eur. J. Med. Chem., 121, 58 (2016); https://doi.org/10.1016/j.ejmech.2016.05.017
T. Mondal, A.V.S. Lavanya, A. Mallick, T.L. Dadmala, R.M. Kumbhare, U. Bhadra and M.P. Bhadra, Apoptosis, 22, 786 (2017); https://doi.org/10.1007/s10495-017-1367-1
Z.Q. Liao, C. Dong, K.E. Carlson, S. Srinivasan, J.C. Nwachukwu, R.W. Chesnut, A. Sharma, K.W. Nettles, J.A. Katzenellenbogen and H.B. Zhou, J. Med. Chem., 57, 3532 (2014); https://doi.org/10.1021/jm500268j
B. Nabuurs, M. Wagener and J. de Vlieg, J. Med. Chem., 50, 6507 (2007); https://doi.org/10.1021/jm070593p
G.M. Sastry, M. Adzhigirey, T. Day, R. Annabhimoju, W. Sherman, J. Comput. Aided Mol. Des., 27, 221 (2013).
R.C. Johnston, K. Yao, Z. Kaplan, M. Chelliah, K. Leswing, S. Seekins, S. Watts, D. Calkins, J. Chief Elk, S.V. Jerome, M.P. Repasky and J.C. Shelley, J. Chem. Theory Comput., 19, 2380 (2023); https://doi.org/10.1021/acs.jctc.3c00044
R.A. Friesner, J.L. Banks, R.B. Murphy, T.A. Halgren, J.J. Klicic, D.T. Mainz, M.P. Repasky, E.H. Knoll, M. Shelley, J.K. Perry, D.E. Shaw, P. Francis and P.S. Shenkin, J. Med. Chem., 47, 1739 (2004); https://doi.org/10.1021/jm0306430
Z. Kaplan, S. Ehrlich and K. Leswing, Benchmark Study of DeepAuto-QSAR, ChemProp and DeepPurpose on the ADMET Subset of the Therapeutic Data Commons, Schrödinger, Inc. (2022); https://www.schrodinger.com/wpcontent/uploads/2023/10/22_086_machine_learning_white_paper_r4-1.pdf
A.S. Shokouhi Asl, S. Ranjbar, M.H. Sayahi, Z. Dehghani, M. Emami, A.M. Taherkhani, M. Negahdaripour, N. Dastyafteh, S. Safapoor, A. Ghahramani, M.R. Mohajeri-Tehrani, B. Larijani, M. Mahdavi and Y. Ghasemi, RSC Adv., 15, 37447 (2025); https://doi.org/10.1039/D5RA02760H
A.M. Malebari, M.A.M. Ali, A. Musa, M.E.A. Zaki, S.M. Gomha, M.A. Soliman, M.A. Abdelgawad, D.G.T. Parambi, M.R. Aouad, H.S. Abulkhair and H.E.A. Ahmed, RSC Adv., 15, 47601 (2025); https://doi.org/10.1039/D5RA07972A
B. Huwaimel, A.S. Abouzied, M.E.A. Zaki, A. Alamri, B. Farag, S. Alqarni and S.M. Gomha, ChemistryOpen., 14, e202500288 (2025); https://doi.org/10.1002/open.202500288
M.N. El-Bayaa, A.M. Srour, A.L. Alanzy, S. Messaoudi, A.A. Abd-Rabou, A. Saleh, M.G.A. Saleh and W.A. El-Sayed, Future Med. Chem., 17, 2927 (2025); https://doi.org/10.1080/17568919.2025.2587567
A.M. Srour, M.N. El-Bayaa, A. Temirak, A.L. Alanzy, H.M. Awad, A. Saleh, M.G. Saleh and W.A. El-Sayed, Sci. Rep., 15, 25514 (2025); https://doi.org/10.1038/s41598-025-96675-3
S. Alqahtani, M.A. Al-Omar, H.A. Ghabbour and A.A. El-Emam, Molecules., 28, 4123 (2023); https://doi.org/10.3390/molecules28104123
