Elton Alisson | Agência FAPESP – Starting in the 1980s, a marine animal popularly known as sun coral (Tubastraea tagusensis) began to be observed off the Brazilian coast, anchored on oil platforms in the Campos Basin, in Rio de Janeiro. Today, this invasive species, originally from the Indo-Pacific, has already spread over more than 3,500 kilometers (km) of the Brazilian coast and is considered a threat to biological diversity because it destroys other coral species, reproduces quickly and does not have a natural predator.
When analyzing the toxins produced by the sun coral to defend itself against predation by fish and other organisms and compete for space and substrates, researchers from the Adolfo Lutz Institute, Federal University of ABC (UFABC) and the Marine Biology Center of the University of São Paulo (Cebimar-USP) found that one of the substances secreted by the animal is capable of combating Trypanosoma cruzi, the parasite that causes Chagas disease.
The results of the study, supported by FAPESP, were described in an article published in the journal ACS Omega, of the American Chemical Society.
“If, on the one hand, the sun coral is a villain for marine biodiversity, on the other hand it has the potential to be beneficial to human life by producing a chemical substance with pharmacological potential to combat a disease that affects 7 million people and requires treatments. effective”, tells André Gustavo Tempone Cardoso, a researcher at the laboratory of new drugs for neglected diseases at the Instituto Adolfo Lutz and coordinator of the project.
The scientist had his first contact with the sun coral in the 1990s, when diving in Ilha Grande, in Angra dos Reis (RJ).
“At the time, I didn’t know that this coral, which is very beautiful, was an invasive species,” says Tempone.
When talking about his impressions about the sun coral with Álvaro Esteves Migotto, the Cebimar researcher and co-author of the study commented that the animal produced toxins that killed other corals found on the Brazilian coast, such as the brain coral (Mussismilia hispida), and that was dominating the seascapes.
Based on this observation, they began to collect samples of the sun coral in the São Sebastião channel, on the north coast of São Paulo, where Cebimar is located, to analyze the chemical compounds produced by the animal.
The study was conducted during Maiara Romanelli Silva’s PhD, first author of the article and Tempone’s supervisor.
“There are many studies on the biology of the sun coral, but there was still no research related to the pharmacological activity of the compounds it produces”, says Tempone.
Through fractionation guided by bioactivity, the researchers identified chemical compounds produced by sun coral with potential antiparasitic action. Using nuclear magnetic resonance techniques and high-resolution mass spectrometry, they were able to isolate and chemically characterize a candidate substance to combat Trypanosoma cruzi.
Studies carried out by researcher João Henrique Ghilardi Lago, a professor at UFABC, made it possible to elucidate the structure of the molecule and identify it as a 6-bromo-2 indole alkaloid of methylaplisoposin.
“This substance belongs to a very interesting class of compounds from a pharmaceutical point of view, as it presents biological activities of interest for the treatment of human diseases”, explains Tempone.
The researchers tested the pure chemical compound against T. cruzi in mammalian cells (in vitro) in the extracellular (trypomastigote) phase – present in the initial phase of Chagas disease, in which the parasite is still circulating in the blood – and intracellular (amastigote). ), present in the chronic phase of the disease, when the parasite disappears from circulation because it has already invaded the cells, especially those of the heart and digestive muscles.
The results of the tests indicated that the compound was able to eliminate the parasite in these two phases, without showing toxic effects on the cells even at the highest concentration tested.
The results of studies on the compound’s mechanisms of action on T. cruzi showed that the substance affects the parasite’s calcium levels, reducing the generation of ATP [adenosine triphosphate] in the mitochondria – the source of cellular energy.
“The compound damages the only mitochondria that the parasite has and which manufactures ATP”, explains Tempone.
Through a computational study (in silico), the similarity of the chemical compound with drugs available on the market for the treatment of Chagas disease was also evaluated, based on their physical-chemical properties and pharmacodynamic parameters.
The analyzes indicated that the compound has similar properties to several approved drugs on the market. One of the only drugs available today for the treatment of the disease is benznidazole, which, despite reducing the burden of T. cruzi in chronic patients, does not prevent heart damage caused by the disease or other symptoms, such as colon enlargement, in addition to to cause serious side effects.
“Now we are dedicated to being able to carry out the total synthesis of compounds derived from this molecule, with greater potency, and to test them in an animal model”, says Tempone.
The article Mitochondrial Imbalance of Trypanosoma cruzi Induced by the Marine Alkaloid can be read at: https://pubs.acs.org/doi/10.1021/acsomega.2c03395
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