Pyrimidine-Piperazine Hybrids as Potential PARP1 Inhibitors:  Dual in silico and in vitro Approaches against Breast Cancer

Rashmi Shivakumar; Narasimha M. Beeraka; Toreshettahally R. Swaroop; Zhang Xi; D.C. Vinay Kumar; Syed Hidayathulla; Basappa Basappa

doi:10.14233/ajchem.2026.35478

Issue

Vol. 38 No. 4 (2026): Vol 38 Issue 4, 2026

Issue Published : 8 April 2026

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

Pyrimidine-Piperazine Hybrids as Potential PARP1 Inhibitors: Dual in silico and in vitro Approaches against Breast Cancer

https://doi.org/10.14233/ajchem.2026.35478

Rashmi Shivakumar

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

https://orcid.org/0009-0007-1932-6149

Narasimha M. Beeraka

Department of Human Anatomy and Histology, I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 8/2 Trubetskaya Str., Moscow 119991, Russia; Saveetha Institute of Basic Medical Sciences (SIBMS), Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai-600077, India

https://orcid.org/0000-0001-6879-7835

Toreshettahally R. Swaroop

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

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

Zhang Xi

Shenzhen Bay Laboratory, Shenzhen-518055, P.R. China

https://orcid.org/0000-0003-4093-0897

D.C. Vinay Kumar

Department of Physics, The National Institute of Engineering North Campus, Mysuru-570008, India

https://orcid.org/0000-0003-2312-5909

Syed Hidayathulla

Department of Studies in Molecular Biology, University of Mysore, Mysuru-570006, India

https://orcid.org/0009-0009-3170-2308

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. 4 (2026): Vol 38 Issue 4, 2026
Article Published : 8 April 2026

Abstract

Pyrimidine derivatives are known to possess notable anticancer properties. In this study, a new series of pyrimidine-piperazine hybrid compounds (8a-j) was synthesised and evaluated for cytotoxic and PARP1 inhibitory activities against MCF-7 breast cancer cells. The IC₅₀ values against this cell line were determined by Alamar blue assay. The poly(ADP-ribose) polymerase-1 (PARP1) catalytic activity was assessed through a fluorescence-based enzymatic assay. Among the synthesised compounds, 8e demonstrated the highest potency with an IC₅₀of 10.45 µM, showing significant PARP1 inhibition. Docking analysis revealed strong and specific binding of 8e to the PARP1 active site, supporting the experimental data.

Keywords

Breast cancer PARP1 Thiouracil Piperazine Anticancer activity Docking studies

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Shivakumar, R.; Beeraka, N. M.; Swaroop, T. R.; Xi, Z.; Vinay Kumar, D.; Hidayathulla, S.; Basappa, B. Pyrimidine-Piperazine Hybrids As Potential PARP1 Inhibitors: Dual in Silico and in Vitro Approaches Against Breast Cancer. ajc 2026, 38, 956-962.

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L. Yin, J.-J. Duan, X.-W. Bian and S.-C. Yu, Breast Cancer Res., 22, 61 (2020); https://doi.org/10.1186/s13058-020-01296-5

J. Pang, N. Ding, X. Liu, X. He, W. Zhou, H. Xie, J. Feng, Y. Li, Y. He, S. Wang and Z. Xiao, Ann. Surg. Oncol., 32, 750 (2025); https://doi.org/10.1245/s10434-024-16454-8

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T.R. Swaroop, Z.-Q. Wang, Q.Y. Li and H.-S. Wang, J. Electrochem. Soc., 167, 046504 (2020); https://doi.org/10.1149/1945-7111/ab72ed

N. Rajeev, T.R. Swaroop, S.M. Anil, K.R. Kiran, K.S. Rangappa and M.P. Sadashiva, J. Chem. Sci., 130, 150 (2018); https://doi.org/10.1007/s12039-018-1540-2

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Dukanya, T.R. Swaroop, K.S. Rangappa and Basappa, Curr. Org. Chem., 24, 2792 (2020); https://doi.org/10.2174/1385272824999201020204001

S.M. Anil, M.S. Sudhanva, T.R. Swaroop, A.C. Vinayaka, N. Rajeev, K.R. Kiran, R. Shobith and M.P. Sadashiva, Chem. Biodivers., 17, e2000014 (2020); https://doi.org/10.1002/cbdv.202000014

R. Huey, G.M. Morris, A.J. Olson and D.S. Goodsell, J. Comput. Chem., 28, 1145 (2007); https://doi.org/10.1002/jcc.20634

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.