Trials involving mammalian cells were conducted by researchers in São Paulo state, Brazil. Although it endangers biodiversity along much of the coast, sun coral could be an ally in combating Chagas disease, which affects 7 million people worldwide and lacks effective treatment (photo: André Tempone)
Published on 07/03/2023
By Elton Alisson | Agência FAPESP – Tubastraea tagusensis, a marine animal popularly known as sun coral, began to be observed on the Brazilian coast in the 1980s, attached to offshore oil rigs in the Campos Basin in Rio de Janeiro state. This invasive species, which originated in the Indo-Pacific, has now spread along the coastline for more than 3,500 km and is considered a threat to biological diversity. It destroys other coral species, reproduces rapidly, and fiercely protects itself from predators.
When researchers in São Paulo state, Brazil, analyzed the toxins produced by T. tagusensis to defend itself against fish and other predatory organisms and to compete for space and substrates, they found that one of the substances it secretes can combat Trypanosoma cruzi, the parasite that causes Chagas disease.
The study was supported by FAPESP and reported in an article published in ACS Omega, a journal of the American Chemical Society (ACS).
“T. tagusensis is a threat to marine biodiversity, but it could be beneficial to humans in light of this chemical substance it produces, which has the potential to be used in a drug to combat a disease that affects 7 million people worldwide and has no effective treatment,” André Gustavo Tempone, last author of the article, told Agência FAPESP.
Tempone is a researcher in the laboratory that looks for drugs to treat neglected diseases at Adolfo Lutz Institute (IAL), the reference laboratory for epidemiological surveillance in São Paulo state. He acts as principal investigator for the project, which also involves researchers at the Federal University of the ABC (UFABC) and the University of São Paulo’s Center for Marine Biology (CEBIMAR-USP).
Tempone first observed T. tagusensis in the 1990s, when he was diving off Ilha Grande, an island in the municipality of Angra dos Reis in Rio de Janeiro state. “At the time, I didn’t know that this coral, which is beautiful to look at, was an invasive species,” he said.
According to Álvaro Esteves Migotto, a co-author of the article and a researcher at CEBIMAR-USP, the group realized that T. tagusensis produced toxins that killed other coral species found on the Brazilian coast, such as the brain coral Mussismilia hispida, and was becoming dominant in the region. Based on this observation, he and Tempone began to collect samples of T. tagusensis in the São Sebastião channel on the northern coast of São Paulo state, where CEBIMAR-USP is located, to analyze the chemical compounds produced by the coral.
The study was conducted during the doctoral research of Maiara Romanelli Silva, first author of the article, whose PhD was supervised by Tempone.
“There are many studies of the biology of T. tagusensis, but before ourselves, no one had investigated the pharmacological activity of the compounds it produces,” Tempone said.
Candidate compound
Using bioactivity-guided fractionation, the researchers found chemical compounds with potential anti-parasite activity produced by the coral. They then used nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) to isolate and chemically characterize a candidate substance to combat T. cruzi.
Studies conducted by João Henrique Ghilardi Lago, a professor at UFABC, elucidated the structure of the molecule, identifying it as indole alkaloid 6-bromo-2′-de-N-methylaplysinopsin.
“This substance belongs to a class of compounds that’s very interesting from the pharmaceutical standpoint because of the relevance of its biological activities to the treatment of human diseases,” Tempone said.
The researchers tested the substance in vitro in its pure state against T. cruzi in mammalian cells in the main infective stage (trypomastigotes) of Chagas disease, when the parasite is still in the bloodstream, and the replicative stage (amastigotes) found once the disease has become chronic, when the parasite disappears from the bloodstream to invade cells in the heart and digestive muscles.
The results of the trials showed that the compound could eliminate the parasite in both stages without toxic effects on cells even at the highest concentrations tested. Analysis of the compound’s action mechanism showed that the substance affected levels of calcium in the parasite, reducing the secretion of adenosine triphosphate (ATP), the source of cellular energy, in its mitochondria.
“The compound damages the only mitochondria the parasite has and its sole source of ATP,” Tempone said.
Through a computational study (in silico), the researchers compared the compound with drugs available on the market for Chagas disease, on the basis of their physicochemical properties and pharmacodynamics. The findings showed that the compound has similar properties to several commercially available drugs. One of the few medications currently available for Chagas disease is benznidazole, which reduces parasite load in chronic patients but does not prevent damage to the heart or other problems, such as colon swelling, and has severe side effects.
“We’re now focusing on synthesizing more potent compounds derived from this molecule and testing them on an animal model,” Tempone said.
The article “Mitochondrial imbalance of Trypanosoma cruzi induced by the marine alkaloid 6-bromo-2’-de-n-methylaplysinopsin" is at: pubs.acs.org/doi/10.1021/acsomega.2c03395.
Source: https://agencia.fapesp.br/41809
