Issue

Vol. 38 No. 8 (2026): Vol 38, Issue 8 (2026)

Copyright (c) 2026 POOJA AGARWAL

Creative Commons License

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

Synthesis and Evaluation of Novel Piperazine Hybrids as Promising Anticancer Agents

https://doi.org/10.14233/ajchem.2026.36213
Vaibhav Daund
Department of Chemistry and Sustainability, School of Basic Sciences, Galgotias University, Greater Noida-203201, India
https://orcid.org/0009-0003-6394-5589
Pooja Agarwal
Department of Chemistry and Sustainability, School of Basic Sciences, Galgotias University, Greater Noida-203201, India
https://orcid.org/0000-0002-5963-5137
Arvind Jain
School of Basic and Applied Sciences, IILM University, Greater Noida-201306, India
https://orcid.org/0000-0001-6062-3718
Pratichi Singh
School of Biosciences and Technology, Galgotias University, Greater Noida-203201, India
https://orcid.org/0000-0002-8163-355X
Ameya Hebale
Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad-121001, India

Corresponding Author(s) : Pooja Agarwal

poojaocm5@gmail.com

Asian Journal of Chemistry, Vol. 38 No. 8 (2026): Vol 38, Issue 8 (2026)

Abstract

This study aimed to synthesise a novel series of piperazine analogues (3a-k) having anticancer potential against MCF-7, MDA-MB-231 and HeLa cell lines. Structure of the synthesised analogues were confirmed through NMR and biological evaluation were done through MTT assay taking doxorubicin as a reference standard. The synthesised derivatives exhibited appreciable cytotoxicity at low concentrations. Molecular docking examined their binding interactions with estrogen receptor-α (ERα) and epidermal growth factor receptor (EGFR), associated with MCF-7 and MDA-MB-231 cell lines, respectively, providing structural insight into their anticancer potential. The results revealed that the synthesised derivative 3h has potential binding affinity hence blocking the activity. Therefore, the results obtained from in vitro and in silico studies identify the synthesised piperazine derivatives as promising lead compounds for further anticancer optimization. The IC50 values support this observation, with compounds 3g, 3h and 3i exhibiting the highest cytotoxic activity among the other derivatives evaluated.

Keywords

Hybrid drug design Piperazine derivatives Breast cancer Cytotoxicity Molecular docking
(1)
Daund, V.; Agarwal, P.; Jain, A.; Singh, P.; Hebale, A. Synthesis and Evaluation of Novel Piperazine Hybrids As Promising Anticancer Agents. ajc 2026, 38, 2117-2124.
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. S. Sari and M. Yilmaz, Turk. J. Chem., 44, 1303 (2020); https://doi.org/10.3906/KIM-2003-23
  2. A.C. Flick, H.X. Ding, C.A. Leverett, R.E. Kyne, K.K.C. Liu, S.J. Fink and C.J. O'Donnell, J. Med. Chem., 60, 6480 (2017); https://doi.org/10.1021/acs.jmedchem.7b00010
  3. L. Wang, R. Li, C. Song, Y. Chen, H. Long and L. Yang, Nat. Prod. Commun., 16, 1934578X211040326 (2021); https://doi.org/10.1177/1934578X211040326
  4. A.C. Flick, C.A. Leverett, H.X. Ding, E. McInturff, S.J. Fink, C.J. Helal and C.J. O'Donnell, J. Med. Chem., 62, 7340 (2019); https://doi.org/10.1021/acs.jmedchem.9b00196
  5. N. Sun, C. Ren, Y. Kong, H. Zhong, J. Chen, Y. Li, J. Zhang, Y. Zhou, X. Qiu, H. Lin, X. Song, X. Yang and B. Jiang, Eur. J. Med. Chem., 193, 112190 (2020); https://doi.org/10.1016/j.ejmech.2020.112190
  6. S. Bedi, S.A. Khan, M.M. AbuKhader, P. Alam, N.A. Siddiqui and A. Husain, Saudi Pharm. J., 26, 755 (2018); https://doi.org/10.1016/j.jsps.2018.04.010
  7. M. Levis and A.E. Perl, Blood Adv., 4, 1178 (2020); https://doi.org/10.1182/BLOODADVANCES.2019000174
  8. Q. Jiang, M. Li, H. Li and L. Chen, Biomed. Pharmacother., 150, 112974 (2022); https://doi.org/10.1016/j.biopha.2022.112974
  9. R. Roskoski, Pharmacol. Res., 187, 106552 (2023); https://doi.org/10.1016/j.phrs.2022.106552
  10. K. Powell and V. Prasad, Transl. Oncol., 14, 101206 (2021); https://doi.org/10.1016/j.tranon.2021.101206
  11. M. Faizan, R. Kumar, A. Mazumder, Salahuddin, N. Kukreti, A. Kumar and M.V.N.L. Chaitanya, Chem. Biol. Drug Design, 103, e14537 (2024); https://doi.org/10.1111/cbdd.14537
  12. M.N. Romanelli, L. Braconi, A. Gabellini, D. Manetti, G. Marotta and E. Teodori, Molecules, 29, 68 (2024); https://doi.org/10.3390/molecules29010068
  13. S. Fortin and G. Bérubé, Expert Opin. Drug Discov., 8, 1029 (2013); https://doi.org/10.1517/17460441.2013.798296
  14. H. Shan, X. Ma, G. Yan, M. Luo, X. Zhong, S. Lan, J. Yang, Y. Liu, C. Pu, Y. Tong and R. Li, Eur. J. Med. Chem., 219, 113432 (2021); https://doi.org/10.1016/j.ejmech.2021.113432
  15. B. Meunier, Acc. Chem. Res., 41, 69 (2008); https://doi.org/10.1021/ar7000843
  16. C. Viegas-Junior, A. Danuello, V. da Silva Bolzani, E.J. Barreiro and C.A.M. Fraga, Curr. Med. Chem., 14, 1829 (2007); https://doi.org/10.2174/092986707781058805
  17. J.K. Ryu, W.J. Lee, K.H. Lee, J.H. Hwang, Y.T. Kim, Y.B. Yoon and C.Y. Kim, Cancer Lett., 237, 143 (2006); https://doi.org/10.1016/j.canlet.2005.05.040
  18. 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
  19. V. Gote, A.R. Nookala, P.K. Bolla and D. Pal, Int. J. Mol. Sci., 22, 4673 (2021); https://doi.org/10.3390/ijms22094673
  20. Q. Wu, Z. Yang, Y. Nie, Y. Shi and D. Fan, Cancer Lett., 347, 159 (2014); https://doi.org/10.1016/j.canlet.2014.03.013
  21. H. Amawi, H.M. Sim, A.K. Tiwari, S.V. Ambudkar and S. Shukla, Adv. Exp. Med. Biol., 1141, 549 (2019); https://doi.org/10.1007/978-981-13-7647-4_12
  22. N.K. Sharma, A. Bahot, G. Sekar, M. Bansode, K. Khunteta, P.V. Sonar, A. Hebale, V. Salokhe and B.K. Sinha, Cancers, 16, 680 (2024); https://doi.org/10.3390/cancers16040680
  23. D.L. Hughes, Org. Process Res. Dev., 23, 2302 (2019); https://doi.org/10.1021/acs.oprd.9b00326
  24. S. Yadaiah, L. Eppakayala, R. Merugu and M. Jyothi, Indian J. Heterocycl. Chem., 30, 319 (2020).
  25. R. Kalariya, D. Ojha, S. Rana, A. Rode, R. Bhosale and J.S. Yadav, Results Chem., 5, 100954 (2023); https://doi.org/10.1016/j.rechem.2023.100954
  26. M. Bugnon, U.F. Röhrig, M. Goullieux, M.A.S. Perez, A. Daina, O. Michielin and V. Zoete, Nucleic Acids Res., 52, W324 (2024); https://doi.org/10.1093/nar/gkae300
  27. N. Kumar, H. K. Gulati, A. Sharma, S. Heer, A.K. Jassal, L. Arora, S. Kaur, A. Singh, K. Bhagat, A. Kaur, H. Singh, J.V. Singh and P.M.S. Bedi, Mol. Divers., 25, 603 (2021); https://doi.org/10.1007/s11030-020-10133-y
  28. L. Kumari, L. Mishra, P. Patel, N. Sharma, G.D. Gupta and B.D. Kurmi, J. Drug Target., 31, 889 (2023); https://doi.org/10.1080/1061186X.2023.2245579
  29. M. Al-Ghorbani, M.A. Gouda, M. Baashen, O. Alharbi, F.A. Almalki and L.V. Ranganatha, Pharm. Chem. J., 56, 29 (2022); https://doi.org/10.1007/s11094-022-02597-z
  30. S. Muhammad, A. Saba, R.A. Khera, A.G. Al-Sehemi, H. Algarni, J. Iqbal, M.Y. Alshahrani and A.R. Chaudhry, Mol. Simul., 48, 1163 (2022); https://doi.org/10.1080/08927022.2022.2072840
  31. J. Szczepanski, D. Khylyuk, A. Korga-Plewko, M. Michalczuk, S. Mandziuk, M. Iwan and N. Trotsko, Int. J. Mol. Sci., 25, 12401 (2024); https://doi.org/10.3390/ijms252212401
  32. B.M. Sanka, D.M. Tadesse, E.T. Bedada, E.T. Mengesha and N. Babu, Bioorg. Chem., 119, 105568 (2022); https://doi.org/10.1016/j.bioorg.2021.105568
  33. B. Ramalingeswara Rao, M. Rao Katiki, D. Kommula, S. Narayanan, R.J. Anto and M.S.R. Murty, Croat. Chem. Acta, 92, 393 (2019); https://doi.org/10.5562/cca3535
  34. I.H. Eissa, A.M. El-Naggar and M.A. El-Hashash, Bioorg. Chem., 67, 43 (2016); https://doi.org/10.1016/j.bioorg.2016.05.006
  35. E. Gurdal, E. Buclulgan, I. Durmaz, R. Cetin-Atalay and M. Yarim, Anti-Cancer Agents Med. Chem., 15, 382 (2015); https://doi.org/10.2174/1871520615666141216151101
Read More
Author biographies is not available.
Crossref
Scopus
Google Scholar
Europe PMC
Download
PDF
Statistic
Read Counter : 19 Download : 5
PlumX