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

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Computational Chemistry

Background:

• The chalcone scaffold pyrazole is a key structure in medicinal chemistry.
• Developing novel anticancer agents is crucial for cancer treatment.

Purpose of the Study:

• To design and synthesize new chalcone-coupled pyrazole derivatives.
• To evaluate the cytotoxic activity and anticancer potential of these novel compounds.

Main Methods:

• Synthesis of chalcone-coupled pyrazole derivatives (1a-1o).
• Characterization using FT-IR, NMR, GC-MS, and elemental analysis.
• In vitro cytotoxic analysis on MCF-7 and HepG2 cancer cell lines.
• Molecular docking, ADMET, and DFT studies.

Main Results:

• Compound 1a exhibited significant cytotoxic activity against MCF-7 cells (LC50, 0.62 ± 0.01 µM), surpassing Doxorubicin.
• Compound 1a showed a higher binding affinity (-10.8 Kcal/mol) in molecular docking compared to Doxorubicin (-4.7 Kcal/mol).
• DFT calculations, including HOMO-LUMO analysis, provided insights into the electronic properties and stability of compound 1a.

Conclusions:

• Compound 1a displays promising potential as an anti-cancer agent.
• The synthesized chalcone-pyrazole derivatives warrant further investigation for therapeutic applications.