Novel lead compounds in pre-clinical development against African sleeping sickness

Abstract

Human African trypanosomiasis (HAT), also known as African sleeping sickness, is caused by parasitic protozoa of the genus . As the disease progresses, the parasites cross the blood brain barrier and are lethal for the patients if the disease is left untreated. Current therapies suffer from several drawbacks due to toxicity of the respective compounds or resistance to approved antitrypanosomal drugs. In this review, the different strategies of drug development against HAT are considered, namely the target-based approach, the phenotypic high throughput screening and the drug repurposing strategy. The most promising compounds emerging from these approaches entering an evaluation are mentioned herein. Of note, it may turn out to be difficult to confirm activity in an animal model of infection; however, possible reasons for the missing efficacy in unsuccessful studies are discussed.

Exploring the Antiplasmodial 2‐Aminopyridines as Potential Antitrypanosomal Agents

“…brucei viability at 10 μM) resulted in a loss of activity. However, other compounds which featured a para-methyl functionality included 2-methyl pyridine (7), and methyl quinoline (8) were found to be moderate or low micromolar inhibitors. Furthermore, 2-methoxy-3-(trifluoromethyl)pyridine (99, 25 % T.b.…”

“…rhodesiense (fast‐progressing) and T.b. gambiense (slow‐progressing) respectively . Despite the infections being clinically distinct, T.b .…”

“…gambiense (slow-progressing) respectively. [6,7] Despite the infections being clinically distinct, T.b. sub-species retain large degrees of homology in their molecular and cellular biology, [8] allowing for the T.b.…”

Synthesis, Structure and In Vitro Anti-Trypanosomal Activity of Non-Toxic Arylpyrrole-Based Chalcone Derivatives

“…Infectious diseases caused by kinetoplastid parasites are a serious health threat worldwide. Among these is human African trypanosomiasis (HAT), commonly referred to as sleeping sickness [1,2]. HAT has also been prioritized by the World Health Organization (WHO) in the list of neglected tropical diseases (NTDs) in 149 endemic countries [3][4][5].…”

Synthesis, Antiplasmodial and Antitrypanosomal Evaluation of a Series of Novel 2-Oxoquinoline-based Thiosemicarbazone Derivatives

“…are Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. 6,7 Up to 70 million people, in various parts of the 36 countries in Africa where the disease is endemic, are at risk of infection. 6 While the cases of HAT in Africa have been reasonably low, in 2015 an estimated 3000 new infections of East and West African trypanosomiasis were reported to the World Health Organisation (WHO).…”