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Amentoflavone, a potent natural matrix metalloproteinase 2 inhibitor
Seri Jo1, Mi-Sun Kim1, Hwa-Young Kim1
1College of Pharmacy and Graduates School of Pharmaceutical Sciences, Ewha W. University, Seoul, Republic of Korea.
Abstract:
Gelatinase A (MMP-2) has been studied and proven to play a vital role in the intrusion and metastasis of cancer. Flavonoids influence on molecular and cellular functions of MMP-2 and thus a systematic investigation of flavonoids against the metalloproteolytic activity of MMP-2 has been performed in this study. A fluorescence resonance energy transfer method was used to investigate the inhibitory activities of various flavonoids. Flavone, flavonol and isobavachalcone derivatives showed their inhibitory activity against MMP-2. Surprisingly, the most effective inhibitor was Amentoflavone and its blocking function was superior to other flavonoids. Its IC50 value was 0.689 μM. An induced-fit docking study was carried out to survey its extraordinary activity. The binding mode of Amentoflavone is quite similar to that of (2 ∼ {S})-2-[2-[4-(4-methoxyphenyl) phenyl] sulfanylphenyl] pentanedioic acid complexed with MMP-9. Amentoflavone interacts with the functional zinc and catalytic residue, Glu202. Therefore, the docking study reasonably confirmed the strong inhibitory activity of Amentoflavone.
Insights
Amentoflavone effectively inhibits cancer-promoting MMP-2 activity. This natural compound shows superior blocking function, offering potential for new cancer metastasis treatments.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Gelatinase A (MMP-2) is crucial for cancer invasion and metastasis.
- Flavonoids modulate MMP-2's molecular and cellular functions.
Purpose of the Study:
- To systematically investigate the inhibitory effects of various flavonoids on MMP-2 metalloproteolytic activity.
- To identify potent flavonoid inhibitors of MMP-2.
Main Methods:
- Fluorescence resonance energy transfer (FRET) assay to measure MMP-2 inhibition.
- Induced-fit docking study to elucidate the binding mechanism of potent inhibitors.
Main Results:
- Flavone, flavonol, and isobavachalcone derivatives demonstrated inhibitory activity against MMP-2.
- Amentoflavone emerged as the most potent inhibitor, with an IC50 value of 0.689 μM.
- Docking studies revealed Amentoflavone binds to the catalytic residue Glu202 and functional zinc, similar to known MMP inhibitors.
Conclusions:
- Amentoflavone exhibits strong inhibitory activity against MMP-2.
- The findings support Amentoflavone as a potential therapeutic agent for targeting cancer metastasis.
