Discovery of MMP1 Inhibitors from Dandelion using Molecular Simulation and Bioactivity Test

MMP1 (matrix metallopeptidase 1) plays a significant role in the degradation of collagen fibres within the extracellular matrix, and has been linked to a multitude of biological processes, including rheumatoid arthritis, osteoarthritis, periodontal disease, and tumor invasion.

In order to discover inhibitors of MMP1 that originate from the phytochemicals of the dandelion (Taraxacum mongolicum Hand.-Mazz.).

The herbal constituents of the dandelion were retrieved from the HERB database. A multifaceted approach including molecular docking, MMP1 enzyme assays, and molecular dynamics simulations was used to identify potential MMP1 inhibitors among the chemical compounds present in the dandelion.

A total of 61 chemical constituents of the dandelion were collated from the HERB database. A potential MMP1 inhibitor was identified through a combination of molecular docking and an MMP1 enzyme bioactivity assay. Cichoric acid demonstrated pronounced inhibitory activity against MMP1, with an IC₅₀ value of 7.81 ± 2.60 μM. Molecular dynamics simulations and binding free energy calculations indicated that the nonpolar interaction energies of LEU181, ARG214, VAL215, HIS218, GLU219, HIS228, PRO238, and SER239 played a primary role in the binding of cichoric acid to MMP1.

The integration of molecular modeling and bioactivity testing proved an effective method for the rapid discovery of targeted small molecule inhibitors. Cichoric acid demonstrated potent MMP1 inhibitory activity and thus represented a promising candidate for further development.