Using 5-Nitroimidazole Derivatives against Neglected Tropical Protozoan Diseases: Systematic Review

Author:

Vichi-Ramírez Micheel M.1ORCID,López-López Edgar2ORCID,Soriano-Correa Catalina3,Barrientos-Salcedo Carolina4ORCID

Affiliation:

1. Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa 91192, Mexico

2. Department of Chemistry and Graduate Program in Pharmacology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City 07000, Mexico

3. Unidad de Química Computacional, Facultad de Estudios Superiores Zaragoza (FES-Zaragoza), Universidad Nacional Autónoma de México (UNAM), Iztapalapa, Mexico City 09230, Mexico

4. Laboratorio de Química Médica y Quimiogenómica, Facultad de Bioanálisis Campus Veracruz, Universidad Veracruzana, Veracruz 91700, Mexico

Abstract

Neglected tropical diseases (NTDs) are a significant global health problem. Additionally, anti-protozoan treatments are toxic, and their therapeutic regimens require prolonged treatment times and high concentrations of the drugs. Additionally, multi-resistant protozoan strains represent an important global emergency that must be addressed. For these reasons, global efforts are being made to identify new drug candidates that are capable of combating these kinds of diseases. This systematic review shows that 5-nitroimidazole derivatives have been successfully used against neglected tropical protozoan diseases (NTPDs), with a specific focus on three diseases: malaria, leishmaniasis, and human trypanosomiasis. Some nitroimidazole derivatives have been repurposed, and an important group of new drugs is available for the treatment of NTPDs. Finally, we address 5-nitroimidazoles using chemoinformatics and medicinal chemistry tools to describe the most recent and promising 5-nitroimidazole derivatives associated with anti-protozoal activity using their published in vitro and in vivo data. We show that 5-nitroimidazoles offer a broader spectrum of activity against a variety of protozoal pathogens. More importantly, these compounds demonstrate a significantly reduced systemic toxicity compared to other nitroimidazoles. This makes them a more favorable option in the treatment of protozoal infections, particularly in scenarios where the patient’s tolerance to drug side effects is a critical concern.

Publisher

MDPI AG

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