# Rosmarinic Acid Present in Lepechinia floribunda and Lepechinia meyenii as a Potent Inhibitor of the Adenylyl Cyclase gNC1 from Giardia lamblia

## TL;DR

Rosmarinic acid from two native Argentinian plants effectively inhibits a key enzyme in Giardia lamblia, offering a potential new treatment for giardiasis.

## Contribution

Rosmarinic acid is identified as a potent and specific inhibitor of the gNC1 enzyme in Giardia lamblia, supported by both in silico and experimental validation.

## Key findings

- Lepechinia floribunda and L. meyenii extracts showed strong gNC1 inhibitory activity with IC50 values of 9 and 31 µg/mL.
- Rosmarinic acid was confirmed as a gNC1 inhibitor with an IC50 of 10.1 µM.
- Molecular interactions between rosmarinic acid and gNC1 were elucidated, revealing the binding mechanism.

## Abstract

Giardiasis is a parasitosis caused by Giardia lamblia with significant epidemiological and clinical importance due to its high prevalence and pathogenicity. The lack of optimal therapies for treating this parasite makes the development of new effective chemical entities an urgent need. In the search for new inhibitors of the adenylyl cyclase gNC1 obtained from G. lamblia, 14 extracts from Argentinian native plants were screened. Lepechinia floribunda and L. meyenii extracts exhibited the highest gNC1 inhibitory activity, with IC50 values of 9 and 31 µg/mL, respectively. In silico studies showed rosmarinic acid, a hydroxycinnamic acid present in both mentioned species, to be a promising anti-gNC1 compound. This result was confirmed experimentally, with rosmarinic acid showing an IC50 value of 10.1 µM. Theoretical and experimental findings elucidate the molecular-level mechanism of rosmarinic acid, pinpointing the key interactions stabilizing the compound–enzyme complex and the binding site. These results strongly support that rosmarinic acid is a promising scaffold for developing novel compounds with inhibitory activity against gNC1, which could serve as potential therapeutic agents to treat giardiasis.