To Explore Potential Inhibitors Against Various Enzymatic Targets of Human African Trypanosomiasis.

Synthetic drugs currently prescribed for the treatment of Human African Trypanosomiasis (HAT) are non-specific, toxic, demand extended therapeutic regimes and are of varying efficacy. Along with the challenging demographic and socio-economic hurdles, the everincreasing risk of drug resistance is another major problem to be addressed. Cysteine protease, Heat shock proteins (HSP-90), Trypanothione reductase (TR), Farnesyl diphosphate synthase, Glucose-6-phosphate dehydrogenase, UP-4-galactose epimerase, and Cytidine triphosphate synthetase are potential enzymatic targets for the development of novel inhibitors against HAT which are the main focus of this review. The potential enzymatic targets of Trypanosoma brucei, especially small molecules like cysteine proteases and heat shock proteins are identified as major candidates for the sustenance of the parasite, their proliferation, infection, and spread of the disease. The development of new compounds to combat the disease by thorough ligand modification has been explored in the current review. Extracting these compounds and studying their efficacy, toxicity, and target mechanism extensively, this review has proposed a list of different compounds, including some synthetic and natural compounds along with multi-target inhibitors such as acoziborole, fexinidazole, etc. Potential inhibitors against these enzymatic targets of the T. brucei are important candidates for designing novel therapeutics against HAT. Multi-target inhibitors have also been identified as crucial molecules because of their potential advantage against the development of drug resistance.

Targeting Cysteine Proteases and their Inhibitors to Combat Trypanosomiasis.

BACKGROUND: Trypanosomiasis, caused by protozoan parasites of the Trypanosoma genus, remains a significant health burden in several regions of the world. Cysteine proteases play a crucial role in the pathogenesis of Trypanosoma parasites and have emerged as potential therapeutic targets for the development of novel antiparasitic drugs. INTRODUCTION: This review article aims to provide a comprehensive overview of the role of cysteine proteases in trypanosomiasis and their potential as therapeutic targets. We discuss the biological significance of cysteine proteases in Trypanosoma parasites and their involvement in essential processes, such as host immune evasion, cell invasion, and nutrient acquisition. METHODS: A comprehensive literature search was conducted to identify relevant studies and research articles on the role of cysteine proteases and their inhibitors in trypanosomiasis. The selected studies were critically analyzed to extract key findings and provide a comprehensive overview of the topic. RESULTS: Cysteine proteases, such as cruzipain, TbCatB and TbCatL, have been identified as promising therapeutic targets due to their essential roles in Trypanosoma pathogenesis. Several small molecule inhibitors and peptidomimetics have been developed to target these proteases and have shown promising activity in preclinical studies. CONCLUSION: Targeting cysteine proteases and their inhibitors holds great potential for the development of novel antiparasitic drugs against trypanosomiasis. The identification of potent and selective cysteine protease inhibitors could significantly contribute to the combat against trypanosomiasis and improve the prospects for the treatment of this neglected tropical disease.