Cinnamic acids as promising bioactive compounds for cancer therapy by targeting MAPK3: a computational simulation...

Area of Science:

• Biochemistry
• Molecular Biology
• Medicinal Chemistry

Background:

• Mitogen-activated protein kinase-3 (MAPK3) is a key regulator in cellular signaling pathways.
• MAPK3 overexpression is implicated in cancer development, metastasis, and drug resistance.
• There is a critical need for novel and effective MAPK3 inhibitors to combat cancer.

Purpose of the Study:

• To identify potential MAPK3 inhibitors from cinnamic acid derivatives.
• To evaluate the binding affinity of cinnamic acids to the MAPK3 active site.
• To explore the therapeutic potential of these compounds in cancer treatment.

Main Methods:

• Computational screening of 20 cinnamic acids against the MAPK3 active site using AutoDock 4.0.
• Ranking compounds based on binding free energy (ΔGbinding).
• Analysis of ligand-receptor interactions using Discovery Studio Visualizer and molecular dynamics simulations.

Main Results:

• Five cinnamic acid derivatives, including cynarin, demonstrated significant binding affinity (ΔGbinding < -10 kcal/mol).
• Cynarin exhibited a picomolar inhibition constant, indicating high potency.
• Molecular dynamics simulations confirmed the stability of the cynarin-MAPK3 complex.

Conclusions:

• Cynarin, chlorogenic acid, rosmarinic acid, caffeic acid 3-glucoside, and cinnamyl caffeate are promising MAPK3 inhibitors.
• These compounds may serve as valuable leads for developing new cancer therapies.
• Targeting MAPK3 with these cinnamic acid derivatives offers a potential strategy for cancer treatment.