Exploring the latest breakthroughs in rhodesain inhibitors for African trypanosomiasis

AbstractHuman African Trypanosomiasis is a serious public health concern, and new chemical therapeutic agents need to be developed to combat this disease. Rhodesain (RhD) inhibitors have shown promising results in medicinal chemistry, specifically againstTrypanosoma brucei. These inhibitors target the cysteine protease RhD, which is essential for the survival ofT. brucei. However, as the pharmaceutical industry lacks interest in these inhibitors, the development of drugs based on them is challenging. In this review, we showed the impact of RhD inhibitors on medicinal chemistry in the past 10 years (2013 –2022), particularly againstT. brucei, showing interesting RhD-based inhibitors, including peptidomimetic inhibitors such as Michael acceptors, cyanide groups, 3-bromoisoxazole, benzodiazepine, among others, as well as non-peptidyl inhibitors. Peptidomimetic inhibitors (5–7,9–15, and17) exhibited the highest potency with respect to dissociation constant (Ki) values for rhodesain, demonstrating promising activity againstT. brucei targeting rhodesain. Thus, we explored recent advancements and perspectives in the context of RhD for potential treatments in sleeping sickness, highlighting its relevance in drug discovery applications.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research