The negatively charged polysaccharide Hyaluronic acid (HA) has diverse physiological and pathophysiological functions depending on its chain size. Space‑filling, anti‑inflammatory and antiangiogenic effects are triggered by high molecular weight HA (HMW HA) (>20 kDa). Hydrolyzation of HMW HA by Hyal‑1 results in low molecular weight HA (LMW HA) (<20 kDa) which leads to inflammatory and angiogenic effects.^[1] For this reason Hyal‑1 is an interesting target for drug discovery. The surface display of active Hyal‑1 on Escherichia coli, via Autodisplay, enables the screening for potential inhibitors in a whole cell system. Based on this technique we determined the inhibitory effect of different natural substances on human Hyal-1. The IC₅₀ values of the plant extracts Malvae sylvestris flos, Equiseti herba and Ononidis radix were determined to be between 1.4 and 1.7 mg/mL. Furthermore, the IC₅₀ values of four triterpenoid saponines were determined. The obtained IC₅₀ value for glycyrrhizinic acid, a known Hyal-1 inhibitor, was 177 µM. The IC₅₀ values for the newly identified inhibitors gypsophila saponin 2, SA1641, and SA1657 were 108 µM, 296 µM and 371 µM, respectively.^[2] For the synthesis of new small molecule inhibitors targeting human Hyal-1 these extracts and natural compounds could be used as a starting point.

References

[1]   Stern R, Semin Cancer Biol, 2008, 18, 275-280.

[2]   Orlando Z, et al. Molecules, 2015, 20, 15449-15498.