0
0
A promising compound derived from Nectandra leucantha, a tree native to southern Brazil, may hold the key to treating visceral leishmaniasis, a neglected tropical disease that remains a significant global health threat. Visceral leishmaniasis, often fatal if untreated, is endemic in Brazil, East Africa, and India, where it affects thousands of people annually. The disease, caused by the Leishmania infantum parasite and transmitted through the bite of sandflies, is characterized by fever, weight loss, anemia, and enlarged organs, leading to death if not addressed.
According to the World Health Organization (WHO), an estimated 50,000 to 90,000 new cases of visceral leishmaniasis and 20,000 to 50,000 deaths occur globally every year, but a large portion of cases remain unreported. The disease disproportionately impacts impoverished regions with inadequate access to health care and sanitation.
In an effort to combat this neglected disease, researchers from Brazil, the United Kingdom, and Portugal have made an exciting breakthrough. A study published in Antimicrobial Agents and Chemotherapy details the development of a compound derived from Nectandra leucantha—locally known as canela-seca or canela-branca. The compound has shown selective activity against Leishmania infantum without damaging host cells, offering hope for a targeted and effective treatment.
The compound’s journey began with the isolation of dehydrodieugenol B, a neolignan from Nectandra leucantha. Researchers, led by João Lago from the Federal University of ABC (UFABC) in Brazil, worked alongside Edward Anderson from the University of Oxford to synthesize the compound. The goal was to design a molecule based on the natural compound and optimize its potency against the parasite.
“We used the substance as a prototype to create variations and test them against the parasite,” explained André Gustavo Tempone, principal investigator of the study and researcher at Butantan Institute in Brazil. Through this iterative process, the team developed a molecule four times more potent than the original.
Despite initial success in vitro, the molecule’s performance in animal trials fell short due to its rapid clearance from the rodents’ systems. This setback led researchers to focus on improving the compound’s bioavailability, ensuring that it remained effective in the animal body for longer periods. After extensive optimization, the team developed a version with a plasma half-life of 21 hours—100 times longer than the initial formulation.
The optimized compound has shown both increased potency and minimal toxicity to host cells. Furthermore, its mechanism of action appears to disrupt the parasite’s energy production by causing an irreversible collapse of ATP synthesis. It also reduces inflammation in host cells, which is a key factor in treating visceral leishmaniasis.
Though the research is promising, the compound’s development is far from complete. In vivo trials with rodents infected with Leishmania are the next step in assessing the compound’s efficacy and necessary dosage. The long-term goal is to bring this compound to market as a medication for visceral leishmaniasis, though experts estimate that the drug development process could take up to 15 years to reach clinical trials.
This research is particularly critical given the lack of interest from large pharmaceutical companies in developing treatments for neglected diseases like visceral leishmaniasis. As Tempone emphasized, Brazil’s biodiversity presents a wealth of potential drug candidates that could address such diseases, but these efforts need significant investment.
“Neglected diseases like visceral leishmaniasis need our attention. If we don’t act, the wealthier countries, where the disease isn’t endemic, likely won’t,” said Tempone.
This discovery highlights the importance of continued research and investment into diseases that disproportionately affect the world’s poorest populations, and offers hope for the future treatment of visceral leishmaniasis.
