Abstract

African trypanosomes cause diseases in humans and livestock. Human African trypanosomiasis is caused by Trypanosoma brucei rhodesiense and T. b. gambiense. Animal trypanosomoses have major effects on livestock production and the economy in developing countries, with disease management depending mainly on chemotherapy. Moreover, only few drugs are available and these have adverse effects on patients, are costly, show poor accessibility, and parasites develop drug resistance to them. Therefore, novel trypanocidal drugs are urgently needed. Here, the effects of synthesized nitrofurantoin analogs were evaluated against six species/strains of animal and human trypanosomes, and the treatment efficacy of the selected compounds was assessed in vivo. Analogs 11 and 12, containing 11- and 12-carbon aliphatic chains, respectively, showed the highest trypanocidal activity (IC50 < 0.34 µM) and the lowest cytotoxicity (IC50 > 246.02 µM) in vitro. Structure-activity relationship analysis suggested that the trypanocidal activity and cytotoxicity were related to the number of carbons in the aliphatic chain and electronegativity. In vivo experiments, involving oral treatment with nitrofurantoin, showed partial efficacy, whereas the selected analogs showed no treatment efficacy. These results indicate that nitrofurantoin analogs with high hydrophilicity are required for in vivo assessment to determine if they are promising leads for developing trypanocidal drugs.

Highlights

  • AAVitro summary of the trypanocidal activity and cytotoxicity data of the nitrofurantoin analogs is shown shown in summary of the activity

  • T. congolense IL3000 and T. b. rhodesiense Chirundu were more sensitive to these nitrofurantoin analogs than the other trypanosome strains/species

  • (1–4) in sub-series decreased with increasing chain lengths up to of four carbons activity relationship within 1the series revealed that the trypanocidal activity short alkyl

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Summary

Introduction

African trypanosomes, transmitted by tsetse fly, cause several diseases in both humans and livestock on the Sub-Saharan African continent. Human African trypanosomiasis (HAT) is caused by Trypanosoma brucei gambiense and T. b. The disease has devastating socio-economic impacts, such as reduced income generation, negative effects on the education of children, increased healthcare costs, and long-term health consequences [1, 2]. Animal African trypanosomosis, which is caused by T. congolense, T. vivax, and T. brucei brucei, represents a major health concern in animal development, and its deleterious impacts can be manifested in terms of reduced livestock productivity, costly disease control, and trade implications, as well as negative impacts on agriculture and Molecules 2021, 26, 3372.

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