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New chalcone tethered pyrazole derivatives: synthesis, molecular docking, ADME-T & DFT study

Year: 2025

Type: article

Abstract: Aim The chalcone scaffold pyrazole is important in organic and medicinal chemistry. This study presents the design and synthesis of new chalcone-coupled pyrazole derivatives (1a-1o). The new compounds were characterized using FT-IR, 1H-NMR, 13C-NMR, GC-MS, elemental analysis, and cytotoxic analysis on MCF-7 and HepG2 cancer cell lines. The synthesized compounds also underwent molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and DFT (density functional theory) studies.Results Compound 1a showed high cytotoxic activity against MCF-7 cells (LC50, 0.62 ± 0.01 µM), outperforming standard Doxorubicin. Compounds were examined using molecular docking, ADME-T, and DFT calculations. Compound 1a had a higher binding affinity (−10.8 Kcal/mol) than Doxorubicin (−4.7 Kcal/mol). ADME-T profile and pharmacokinetic predictions were performed on the analogs. DFT with the B3LYP/6–311++G (DP) basis set helped determine optimal shape and dimensions. Additional Gaussian 16-based DFT calculations were conducted on compounds (1a-1o). The HOMO-LUMO analysis revealed compound 1a had a significant energy gap (2.5056 eV, from −7.94026 eV to −5.43465 eV).Conclusion Compound 1a may be a promising anti-cancer agent.

Source: Future Medicinal Chemistry

DOI: 10.1080/17568919.2025.2580914

Authors: Subramanian Abarna, Surendrakumar Radhakrishnan, D. Sangeetha, Kholood A. Dahlous, Mohammad Shahidul Islam

Institutions: Vellore Institute of Technology University, Bharathidasan University, King Saud University

Language: English

Topic: Synthesis and biological activity

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green

Funder: King Saud University