2. Academic Validation
  3. Design and development of new substituted pyrimidine hybrids with imidazole and triazole: Exploring utility as an anticancer agent via human topoisomerase-II and tubulin inhibition

Design and development of new substituted pyrimidine hybrids with imidazole and triazole: Exploring utility as an anticancer agent via human topoisomerase-II and tubulin inhibition

  • Bioorg Chem. 2025 Mar 1:158:108334. doi: 10.1016/j.bioorg.2025.108334.
Umesh Prasad Yadav 1,  Muhammad Yaseen 2,  Shareen Singh 3,  M Arockia Babu 4,  Mashooq Ahmad Bhat 5,  Roshan Kumar 6,  Yogita Tyagi 7,  Ihsan Ullah 2,  Yaxun Huang 8
Affiliations

Affiliations

  • 1 Department of Hematologic Malignancies Translational Science, City of Hope, Duarte, CA, USA 91010.
  • 2 Institute of Chemical Sciences, University of Swat, Charbagh, 19130, Swat, Pakistan.
  • 3 Centre of Research Impact and Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura- 140401, Punjab, India.
  • 4 Institute of Pharmaceutical Research, GLA University, Mathura 281406, (Uttar Pradesh), India.
  • 5 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
  • 6 Department of Microbiology, Graphic Era (Deemed to be University), Clement Town, Dehradun-248002, India.
  • 7 Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Premanagar, Dehradun 248007, Uttarakhand, India.
  • 8 Department of Liver Transplantation, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. Electronic address: yaxunhuang@csu.edu.cn.
PMID: 40058226 DOI: 10.1016/j.bioorg.2025.108334
Abstract

In the present research, we developed pyrimidine-based hybridized molecules with either imidazole or triazole to find effective Anticancer drugs. The reaction was accomplished using a multicomponent reaction pathway. The synthetics were explored for their utility as an Anticancer agent via human topoisomerase-II and tubulin inhibition. Among the synthetics, compounds 1B4, 1B5, and 1B6 were potent Anticancer agents tested in five Cancer cell lines compared to colchicine and etoposide employed as positive controls. These synthetics were found further devoid of any significant cytotoxicity towards normal cells, thus proving their selective Anticancer nature. Further, these compounds inhibited both the tubulin and hTopoII as indicated by in vitro-based assay. The mechanistic insights were corroborated using molecular docking studies. Besides this, the molecules were found to portray their secondary Anticancer cell death mechanism via Apoptosis. They decreased the oxidative stress, induced Apoptosis, and arrested the cell cycle arrest at the G2/M phase in Cancer cells.

Keywords

Cancer; Drug discovery; Hybrid drug; Pyrimidine; Topoisomerase; Tubulin.

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