Piperazine-Pyrrolidone Acyl Hydrazide Hybrids as New Anticancer Agents against Breast Cancer

Dileep Nagaraju; Mamatha S. Kempasiddegowda; Mahesha Kumaraswamy; Bhoomika B. Ravi; H.S. Monisha Yadav; Toreshettahally R. Swaroop; Santosh L. Goankar; Basappa Basappa

doi:10.14233/ajchem.2026.36108

Issue

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

Issue Published : 7 August 2026

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

Piperazine-Pyrrolidone Acyl Hydrazide Hybrids as New Anticancer Agents against Breast Cancer

https://doi.org/10.14233/ajchem.2026.36108

Dileep Nagaraju

Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysuru-570006, India

https://orcid.org/0009-0004-8596-1640

Mamatha S. Kempasiddegowda

Tsinghua-Berkeley Shenzhen Institute and The Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen-518055, People’s Republic of China

https://orcid.org/0009-0004-3821-5338

Mahesha Kumaraswamy

Department of Chemistry, Sri Mahadeshwara Government First Grade College, Kollegala-571440, India

https://orcid.org/0009-0007-2645-7374

Bhoomika B. Ravi

Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysuru-570006, India

https://orcid.org/0009-0000-0546-4478

H.S. Monisha Yadav

Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysuru-570006, India

https://orcid.org/0009-0009-1694-6400

Toreshettahally R. Swaroop

Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysuru-570006, India

https://orcid.org/0000-0002-0087-6331

Santosh L. Goankar

Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal-576104, India

https://orcid.org/0000-0003-2687-6927

Basappa Basappa

Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysuru-570006, India

https://orcid.org/0000-0002-8844-468X

Corresponding Author(s) : Basappa Basappa

salundibasappa@gmail.com

Asian Journal of Chemistry, Vol. 38 No. 8 (2026): Vol 38, Issue 8 (2026)
Article Published : 7 August 2026

Abstract

Present work describes the development and evaluation of novel piperazine–pyrrolidone acyl hydrazide hybrids as potential anticancer agents for breast cancer treatment. The cytotoxic activities of these compounds were determined against human breast cancer cell lines (MCF-7) by alamar blue assay. A compound 1-(4-(4-chloro-2-fluorophenyl)piperazin-1-yl)-5-oxopyrrolidine-3-carbohydrazide (7b) showed the highest cytotoxicity with IC₅₀ value of 1.46 µM. The lead candidate exhibited superior activity compared to the standard drug tamoxifen (1.75 µM) and was approximately two-fold less potent than doxorubicin (0.73 µM). A structure–activity relationship (SAR) analysis was carried out to understand the effect of structural modifications on anticancer activity. The findings suggest that the lead molecule induces apoptosis in cancer cells by inhibiting the interaction between BCL-XL and BAD, a mechanism supported by in silico studies.

Keywords

Piperazine Pyrrolidone Acyl hydrazide Anticancer Breast cancer Cytotoxic Docking studies

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Nagaraju, D.; Kempasiddegowda, M. S.; Kumaraswamy, M.; Ravi, B. B.; Yadav, H. M.; Swaroop, T. R.; Goankar, S. L.; Basappa, B. Piperazine-Pyrrolidone Acyl Hydrazide Hybrids As New Anticancer Agents Against Breast Cancer. ajc 2026, 38, 2102-2108.

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S. Singh, R. Kumar, S. Tripathi, A. Salahuddin, A. Mazumder and N. Singh, Chem. Biol. Drug Des., 105, e70077 (2025); https://doi.org/10.1111/cbdd.70077

A.A. Bhat, I. Singh, N. Tandon and R. Tandon, Eur. J. Med. Chem., 246, 114954 (2023); https://doi.org/10.1016/j.ejmech.2022.114954

Y. Biliz, B. Hasdemir, H. Başpınar Küçük, M. Zaim, A.M. Şentürk, A. Müdüroğlu Kırmızıbekmez and İ. Kara, ACS Omega, 8, 20073 (2023); https://doi.org/10.1021/acsomega.3c02361

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H.B. Harsha, S. Rangappa, H.D. Preetham, T.R. Swaroop, M. Gilandoust, K.S. Rakesh and K.S. Rangappa, ChemistrySelect, 3, 5228 (2018); https://doi.org/10.1002/slct.201800053

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R. Roopashree, C.D. Mohan, T.R. Swaroop, S. Jagadish and K.S. Rangappa, Asian J. Pharm. Clin. Res., 7, 309 (2014).

Y.H. Lee, S. Lee, J. Sim, E. S. Jo, J.-K. Jung, S. Hyun and J.-H. Kwak, Bull. Korean Chem. Soc., 47, 333 (2026); https://doi.org/10.1002/bkcs.70101

H.M. Poh, Y.S. Chiou, Q.Y. Chong, R.M. Chen, K.S. Rangappa, L. Ma, T. Zhu, A.P. Kumar, V. Pandey, S. Basappa, S.-C. Lee and P. Lobie, Cancers, 11, 1528 (2019); https://doi.org/10.3390/cancers11101528

M. Gilandoust, K.B. Harsha, C.D. Mohan, A.R. Raquib, S. Rangappa, V. Pandey, P.E. Lobie, Basappa and K.S. Rangappa, Bioorg. Med. Chem. Lett., 28, 2314 (2018); https://doi.org/10.1016/j.bmcl.2018.05.020

Q.Y. Chong, M.L. You, V. Pandey, A. Banerjee, Y.J. Chen, H.M. Poh, M. Zhang, L. Ma, T. Zhu, S. Basappa, L. Liu and P.E. Lobie, Oncotarget, 8, 74188 (2017); https://doi.org/10.18632/oncotarget.18431

D.S. Goodsell, M.F. Sanner, A.J. Olson and S. Forli, Protein Sci., 30, 31 (2021); https://doi.org/10.1002/pro.3934

M.D. Hanwell, D.E. Curtis, D.C. Lonie, T. Vandermeersch, E. Zurek and G.R. Hutchison, J. Cheminform., 4, 17 (2012); https://doi.org/10.1186/1758-2946-4-17

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E.F. Pettersen, T.D. Goddard, C.C. Huang, G.S. Couch, D.M. Greenblatt, E.C. Meng and T.E. Ferrin, J. Comput. Chem., 25, 1605 (2004); https://doi.org/10.1002/jcc.20084

Author biographies is not available.