Outlining the Molecules Tested In Vivo for Chagas Disease, Malaria, and Schistosomiasis Over the Last Six Years - A Literature Review Focused on New Synthetic Drug Identities and Repurposing Strategies

Abstract

Background: COVID-19 disrupted NTD programs in 60% of countries, impairing public health goals. Thus, boosting NTD's research knowledge is pressing, and in vivo screening of candidates allows for the prospect of auspicious options based on their overall profile Objective: In this work, we highlighted the relevant research done between 2015-2021 in the fields of synthetic and repurposed drugs that were tested in vivo for Chagas disease, malaria, and schistosomiasis. Methods: MEDLINE, PUBMED, CAPES PERIODIC, and ELSEVIER databases were used for a comprehensive literature review of the last 5 years of research on each area/disease. Results: Overall, research focused on nitro heterocyclic, aromatic nitro, nucleoside, and metal-based scaffolds for analogue-based drug generation. Repurposing was widely assessed, mainly with heterocyclic drugs, their analogues, and in combinations with current treatments. Several drug targets were aimed for Chagas treatment, specific ones such as iron superoxide dismutase, and more general ones, such as mitochondrial dysfunction. For malaria, hemozoin is still popular, and for schistosomiasis, more general structural damage and/or reproduction impairment were aimed at in vitro analysis of the mechanism of action. Conclusion: Latest in vivo results outlined trends for each disease - for Chagas Disease, heterocyclics as thiazoles were successfully explored; for Malaria, quinoline derivatives are still relevant, and for schistosomiasis, repurposed drugs from different classes outstood in comparison to synthetic compounds. This study uprises the continuous development of Chagas disease, malaria, and schistosomiasis drugs, providing researchers with tools and information to address such unmet therapeutic needs.

Chagas Disease across the Ages: A Historical View and Commentary on Navigating Future Challenges

“…In addition, the development of drug resistance, in conjunction with the fact that Nifurtimox and Benznidazole are considered as “obsolete” urge the development of new alternative [ 20 ]. New therapeutic options involving new or repurposed drugs [ 21 , 22 , 23 ] are urgently needed. Fexinidazole is undergoing clinical trials for the treatment of (NCT03587766), and the oxaborole DNDI-6148 has been nominated as a clinical candidate for the treatment of Chagas disease and is in phase I clinical trials (EudraCT 2018-004023-37) [ 24 ].…”