ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Synthesis, docking, molecular dynamics, and biological evaluation of new hybrid dihydropyridine-pyrazole derivatives against breast cancer

Tahseen S. F. Al-Mathkuri, Hamsa H. Al-Hujaj, Rehab G. Abood, Eman Santali, Ahmed A. Majed, and Radwan Alnajjar

Department of Chemistry, College of Science, University of Misan, Misan, Iraq

E-mail: Radwan.alnajjar@uob.edu.ly

Received: 6 July 2025  Accepted: 7 December 2025

Abstract:

Breast cancer (BC) is the most prevalent cancer diagnosed in women, accounting for more than 1 in 10 new cancer diagnoses each year. Even though chemotherapy is successful in breast cancer treatments, resistance to spreading these medications requires a new therapy. Herein, in the extension of our previous work (Al-Mathkuri et al. in J Mol Struct 1321:139704, 2025. https://doi.org/10.1016/j.molstruc.2024.139704), a new series of hybrid dihydropyridine-pyrazole derivatives was synthesized and characterized using spectroscopic techniques, including ¹H NMR, ¹³C NMR, FTIR, and mass spectroscopy. The activity of these compounds as anti-breast cancer agents was estimated against MCF7; most compounds showed IC₅₀ values lower than Uracil (IC₅₀ = 98.10 μg/ml), with compound P5 exhibiting an IC₅₀ of 24.53 μg/ml. Molecular docking against EGFR, HER2, and HERT798I showed that P5 and P8 were more active than the co-crystal drug, with docking scores of − 6.75 and − 6.34 kcal/mol, respectively. Molecular dynamic simulations were implemented to study the stability of the top-runner compounds inside the activity site of the aforementioned targets. It was found that P5 was stable within the three targets. Finally, ADME profiling revealed that compound P5 has high GI absorption and no BBB permeability. These outcomes provide a key milestone in the search for new anti-breast cancer agents.

Keywords: Dihydropyridine; Pyrazole; HER-2; Lapatinib resistance; MCF7

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04581-9

Chemical Papers 80 (5) 4701–4719 (2026)