Glycolic acid (GA) (2-Hydroxyethanoic acid) is widely used as chemical peeling agent in Dermatology and, more recently, as a therapeutic and cosmetic compound in the field of
skin care and disease treatment. In this work we tested the inhibitory ability of
glycolic acid on the enzymatic, hemorrhagic and
edema-inducing activities of BaP1, a P-I
metalloproteinase from Bothrops asper
venom, which induces a variety of
toxic actions.
Glycolic acid inhibited the proteolytic activity of BaP1 on
azocasein, with an IC₅₀ of 1.67 mM. The compound was also effective at inhibiting the hemorrhagic activity of BaP1 in skin and muscle in experiments involving preincubation of
enzyme and inhibitor prior to injection. When BaP1 was injected i.m. and then, at the same site, different concentrations of
glycolic acid were administered at either 0 or 5 min, 7 mM solutions of the inhibitor partially abrogated hemorrhagic activity when administered at 0 min. Moreover,
glycolic acid inhibited, in a concentration-dependent manner,
edema-forming activity of BaP1 in the footpad. In order to have insights on the mode of action of
glycolic acid, UV-vis and intrinsic fluorescence studies were performed. Results of these assays suggest that
glycolic acid interacts directly with BaP1 and chelates the Zn²⁺ ion at the active site. These findings were supported by molecular docking results, which suggested that
glycolic acid forms hydrogen bonds with residues Glu143, Arg110 and Ala111 of the
enzyme. Additionally, molecular modeling results suggest that the inhibitor chelates Zn²⁺, with a distance of 3.58 Å, and may occupy part of substrate binding cleft of BaP1. Our results suggest that
glycolic acid is a candidate for the development of inhibitors to be used in
snakebite envenomation.