Design, Synthesis and Anti-Breast Cancer Activity of New  Benzimidazole-1,2,4-thiadiazoles-benzamide Hybrids

Saritha Sheelam; Jyothi Mandala

doi:10.14233/ajchem.2026.36472

Issue

Vol. 38 No. 9 (2026): Vol 38 Issue 9 Year 2026

Issue Published : 5 September 2026

This work is licensed under a Creative Commons Attribution 4.0 International License.

Design, Synthesis and Anti-Breast Cancer Activity of New Benzimidazole-1,2,4-thiadiazoles-benzamide Hybrids

https://doi.org/10.14233/ajchem.2026.36472

Saritha Sheelam

Department of Chemistry, Mahatma Gandhi University, Nalgonda-508254, India; Department of Chemistry, Govt. Polytechnic College for Women, Suryapet-508213, India

https://orcid.org/0009-0003-9121-6949

Jyothi Mandala

Department of Chemistry, Mahatma Gandhi University, Nalgonda-508254, India

https://orcid.org/0009-0009-3623-4064

Corresponding Author(s) : Jyothi Mandala

jyothimandalamgu@gmail.com

Asian Journal of Chemistry, Vol. 38 No. 9 (2026): Vol 38 Issue 9 Year 2026
Article Published : 5 September 2026

Abstract

A new series of benzimidazole-1,2,4-thiadiazole-benzamide hybrids (7a-l) was synthesized and characterized. The synthesized hybrids were evaluated for anticancer activity against two breast cancer cell lines, MCF-7 and MDA-MB-231, using the MTT assay, with Erlotinib as the reference drug. The results revealed that hybrid 7i exhibited more potent activity against both tested cancer cell lines than the standard drug Erlotinib. The other three hybrids, 7j, 7k and 7l, displayed activity values close to that of the standard drug. Based on these findings, hybrids 7i, 7j, 7k and 7l were further evaluated for tyrosine kinase EGFR inhibitory activity using Erlotinib as the reference drug. Hybrids 7i and 7j exhibited higher EGFR inhibitory activity than erlotinib. Molecular docking studies of the potent hybrids with the EGFR receptor supported the biological results, with hybrids 7i and 7l exhibiting strong interactions with the EGFR protein and superior binding affinities compared with erlotinib. The combined anticancer, EGFR inhibitory and docking results identify hybrid 7i as the most promising hybrid, while hybrids 7j and 7l represent potential EGFR-targeting anticancer candidates.

Keywords

Benzimidazolo-1,2,4-thiadiazolo-benzamide hybrids Anticancer activity EGFR activity Molecular docking studies

(1)

Sheelam, S.; Mandala, J. Design, Synthesis and Anti-Breast Cancer Activity of New Benzimidazole-1,2,4-Thiadiazoles-Benzamide Hybrids. ajc 2026, 38, 2419-2426.

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A.J. Robles, S. Mc Cowen, S. Cai, M. Glassman, R.H. Cichewicz, F. Ruiz II, S.F. McHardy and S.L. Mooberry, J. Med. Chem., 60, 9275 (2017); https://doi.org/10.1021/acs.jmedchem.7b01228

N. Shrivastava, M.J. Naim, M.J. Alam, F. Nawaz, S. Ahmed and O. Alam, Arch. Pharm, 350, 201700040 (2017); https://doi.org/10.1002/ardp.201700040

V.N. Madia, A. Messore, L. Pescatori, F. Saccoliti, V. Tudino, A. De Leo, M. Bortolami, L. Scipione, R. Costi, S. Rivara, L. Scalvini, M. Mor, F.F. Ferrara, E. Pavoni, G. Roscilli, G. Cassinelli, F.M. Milazzo, G. Battistuzzi, R. Di Santo and G. Giannini, J. Med. Chem., 61, 6918 (2018); https://doi.org/10.1021/acs.jmedchem.8b00908

A. Messore, V.N. Madia, L. Pescatori, F. Saccoliti, V. Tudino, A. De Leo, M. Bortolami, D. De Vita, L. Scipione, F. Pepi, R. Costi, S. Rivara, L. Scalvini, M. Mor, F.F. Ferrara, E. Pavoni, G. Roscilli, G. Cassinelli, F.M. Milazzo, G. Battistuzzi, R. Di Santo and G. Giannini, J. Med. Chem., 61, 10834 (2018); https://doi.org/10.1021/acs.jmedchem.8b01497

R. Reddyrajula, P.V. Kathirvel and N. Shankaraiah, Bioorg. Med. Chem. Lett., 122, 130167 (2025); https://doi.org/10.1016/j.bmcl.2025.130167

P. Suresh, N. Srinivas, V. Ravinder, A. Kamal and K. Shravan Kumar, Bioorg. Med. Chem. Lett., 29, 2153 (2019); https://doi.org/10.1016/j.bmcl.2019.06.060

T.R. Deshmukh, A.P. Sarkate, D.K. Lokwani, S.V. Tiwari, R. Azad and B.B. Shingate, Bioorg. Med. Chem. Lett., 29, 126618 (2019); https://doi.org/10.1016/j.bmcl.2019.08.022

X.-H. Yang, L. Xiang, X. Li, T.-T. Zhao, H. Zhang, W.-P. Zhou, X.-M. Wang, H.-B. Gong and H.-L. Zhu, Bioorg. Med. Chem., 20, 2789 (2012); https://doi.org/10.1016/j.bmc.2012.03.040

C.A.G.N. Montalbetti and V. Falque, Tetrahedron, 61, 10827 (2005); https://doi.org/10.1016/j.tet.2005.08.031

J.W. Bode, Curr. Opin. Drug Discov. Dev., 9, 765 (2006).

T. Cupido, J. Tulla-Puche, J. Spengler and F. Albericio, Curr. Opin. Drug Discov. Dev., 10, 768 (2007).

A.K. Ghose, V.N. Viswanadhan and J.J. Wendoloski, J. Comb. Chem., 1, 55 (1999); https://doi.org/10.1021/cc9800071

R.M. Kassab, S.M. Gomha, S.A. Al-Hussain, A.S. Abo Dena, M.M. Abdel-Aziz, M.E.A. Zaki and Z.A. Muhammad, Arab. J. Chem., 14, 103396 (2021); https://doi.org/10.1016/j.arabjc.2021.103396

B.S. Chhikara, N. St. Jean, D. Mandal, A. Kumar and K. Parang, Eur. J. Med. Chem., 46, 2037 (2011); https://doi.org/10.1016/j.ejmech.2011.02.056

A. Ali, D. Bansal, N.K. Kaushik, N. Kaushik, E. Choi and R. Gupta, J. Chem. Sci., 126, 1091 (2014); https://doi.org/10.1007/s12039-014-0671-3

A. Huczyński, G. Klejborowska, M. Antoszczak, E. Maj and J. Wietrzyk, Bioorg. Med. Chem. Lett., 25, 4539 (2015); https://doi.org/10.1016/j.bmcl.2015.08.067

Y. Li, J. Geng, Y. Liu, S. Yu and G. Zhao, ChemMedChem, 8, 27 (2013); https://doi.org/10.1002/cmdc.201200355

Z. Wu, F. Xia and R. Lin, J. Hematol. Oncol., 17, 119 (2024); https://doi.org/10.1186/s 13045-024-01640-8

H. Sung, J. Ferlay, R.L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal and F. Bray, CA Cancer J. Clin., 71, 209 (2021); https://doi.org/10.3322/caac.21660

A. Saini, M. Kuma, S. Bhatt, V. Saini and A. Malik, Int. J. Pharm. Sci. Res., 7, 3121 (2020); https://doi.org/10.13040/IJPSR.0975-8232.11(7).3109-22

S. Morgan, P. Grootendorst, J. Lexchin, C. Cunningham and D. Greyson, Health Policy, 100, 4 (2011); https://doi.org/10.1016/j.healthpol.2010.12.002

L. Rong, N. Li and Z. Zhang, J. Exp. Clin. Cancer Res., 41, 142 (2022); https://doi.org/10.1186/s13046-022-02349-7

M.F. Zayed and M.H. Hassan, Saudi Pharm. J., 22, 157 (2014); https://doi.org/10.1016/j.jsps.2013.03.004

D. Zhang, G. Luo, X. Ding and C. Lu, Acta Pharm. Sin. B, 2, 549 (2012); https://doi.org/10.1016/j.apsb.2012.10.004

Author biographies is not available.

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