# Plant-Derived Lapachol Analogs as Selective Metalloprotease Inhibitors Against Bothrops Venom: A Review

## TL;DR

This paper reviews plant-derived compounds, like lapachol analogs, that selectively inhibit snake venom metalloproteases, potentially offering new treatments for snakebite-induced hemorrhage.

## Contribution

The study highlights new synthetic naphthoquinones that selectively inhibit Bothrops venom metalloproteinases without affecting other venom enzymes.

## Key findings

- Lapachol analogs show selective inhibition of Bothrops venom metalloproteases.
- These compounds do not interfere with phospholipase activity, making them specific for hemorrhagic effects.
- Plant-derived compounds may serve as a basis for developing new antivenom treatments.

## Abstract

Plant compounds that inhibit snake venom activities are relevant and can provide active molecules to counteract snake venom effects. Numerous studies on snake viperid venoms found that metalloproteinases play a significant role in the pathophysiology of hemorrhage that occurs on envenomation. Preclinical studies using vitro and in vivo protocols investigated natural compounds and viperid snake venoms, evaluating the enzymatic, procoagulant, hemorrhagic, edematogenic, myotoxic, and lethal activities. Many studies focused on Bothrops venoms and ascribed that angiorrhexis and hemorrhage resulted from the metalloproteinase action on collagen in the basal lamina. This effect resulted in a combined action with phospholipase A2 and hyaluronidase, inducing hemorrhage, edema, and necrosis. Due to the lack of efficient antivenoms in remote areas, traditional native plant treatments remain common, especially in the Amazon. Our group studied plant extracts, isolated compounds, and lapachol synthetic derivative analogs with selective inhibition for Bothrops venom proteolytic and hemorrhagic activity and devoid of phospholipase activity. We highlight those new synthetic naphthoquinones which inhibit snake venom metalloproteinases and that are devoid of other venom enzyme inhibition. This review shows the potential use of snake venom effects, mainly Bothrops venom metalloproteinase activity, as a tool to identify and develop new active molecules against hemorrhagic effects.