From the 1980s onwards, 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 the Rio de Janeiro. Today, this invasive species, originally from the Indo-Pacific, has already spread over 3,500 km of the Brazilian coast and is considered a threat to biological diversity for destroying other coral species, reproducing quickly and not having 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 Instituto Adolfo Lutz, Universidade Federal do ABC (UFABC) and Center for Marine Biology at 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 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 fight a disease that affects 7 million people and needs treatments effective”, tells Agência FAPESP André Gustavo Tempone Cardoso researcher at the laboratory of new drugs for neglected diseases at Instituto Adolfo Lutz and project coordinator.
The scientist had his first contact with the sun coral in the 1990s, when diving in Big Island 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 your impressions of 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 it was dominating the marine landscapes.
Based on this observation, they began to collect samples of the sun coral in the São Sebastião channel, 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 doctorate, 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”, states Tempone.
Candidate compound
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 conducted by the researcher João Henrique Ghilardi Lago a professor at UFABC, allowed us to elucidate the structure of the molecule and identify it as an indole alkaloid 6-bromo-2 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.
Os researchers tested the pure chemical compound against T. cruzi in mammalian cells (in vitro) in the extracellular (trypomastigote) —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 the circulation because it has already invaded the cells, mainly 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 of the compound’s mechanisms of action on T. cruzi showed that the substance affects the parasite’s calcium levels, reducing the generation of ATP in the mitochondria [adenosina trifosfato] —the source of cellular energy.
“The compound damages the only mitochondria that the parasite has and that 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 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 achieving the total synthesis of compounds derived from this molecule, with greater potency, and testing them in an animal model”, says Tempone.
O artigo Mitochondrial Imbalance of Trypanosoma cruzi Induced by the Marine Alkaloid 6â??Bromo-2-deâ??Nâ??Methylaplysinopsin can be read here.