# Anthonoic Acids A–C, Sulfated and N-(2-Hydroxyethyl)-Substituted Lipidic Amino Acids from the Marine Sponge Antho ridgwayi with In Vitro Cytoprotective Activities

## TL;DR

Scientists discovered new amino acid compounds from a marine sponge that protect cells from damage through specific biological pathways.

## Contribution

The discovery of sulfated and N-(2-hydroxyethyl)-substituted lipidic amino acids with novel cytoprotective mechanisms.

## Key findings

- Anthonoic acids A–C protect cells from hypoxia and ischemia/reperfusion damage via the Nrf2-mediated pathway.
- These compounds reduce ROS levels and upregulate SOD activity without activating NF-κB.
- Anthonoic acids inhibit ATP-induced cell damage and calcium influx, suggesting P2X7 receptor involvement.

## Abstract

Anthonoic acids A–C (1–3), the first representatives of sulfated and N-(2-hydroxyethyl)-substituted lipidic α-amino acids, were isolated along with their plausible precursor, anthamino acid A (4), from the marine sponge Antho ridgwayi. The structures of these compounds were determined using the analysis of 1D and 2D NMR and HR ESI mass spectra. A structural feature of 1–4, compared to all previously known lipidic amino acids, is the presence of a sulfate group near the end opposite the amino acid terminus. At a concentration of 1 µM, anthonoic acids A–C (1–3) effectively protected H9c2 and SH-SY5Y cells in biotests, which modeled hypoxia induced by the addition of CoCl2 to the medium and damage caused by ischemia/reperfusion. These natural products act via the Nrf2-mediated pathway by reducing intracellular ROS levels, accompanied by the upregulation of SOD activity, which is controlled by the Nrf2 transcriptional factor. Anthonoic acids A–C (1–3) do not activate the transcriptional activity of NF-κB but inhibit ATP-induced cell damage and calcium influx, indicating the involvement of P2X7 receptors in the cytoprotective effect of anthonoic acids A–C.