To Explore Potential Natural Inhibitors of Cysteine Proteases to Combat Human African Trypanosomiasis and Chagas Disease.

BACKGROUND: Human African Trypanosomiasis (HAT), also known as sleeping sickness, and Chagas disease are neglected tropical diseases caused by Trypanosoma brucei and Trypanosoma cruzi, respectively. These diseases present significant challenges in treatment due to the toxicity, low efficacy, and drug-resistant strains associated with current therapies. INTRODUCTION: Cysteine proteases play vital roles in the life cycles of these parasites, making them potential targets for therapeutic intervention. Natural inhibitors sourced from plants, marine organisms, and microorganisms show promise for developing novel therapies. METHODS: This review surveys the potential of natural inhibitors as therapeutic agents against HAT and Chagas disease. It compiles PubMed and PubChem information from various studies to provide an overview of their activities and characteristics, including their ability to inhibit cysteine proteases, modulate the host immune response, and interfere with other parasite proteins. RESULTS: Several natural inhibitors, such as berberine, curcumin, and tannins, have been identified and characterized. These inhibitors have demonstrated encouraging outcomes in both in vitro and in vivo experiments, indicating their potential as therapeutic agents for HAT and Chagas disease. CONCLUSION: Natural inhibitors of cysteine proteases offer a promising avenue for developing novel therapies against HAT and Chagas disease. Further research is needed to identify additional natural inhibitors and optimize their efficacy and safety for human use. The significance of this study lies in its potential to contribute to the discovery of effective, safe, and affordable treatments for these neglected tropical diseases.

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.

A new approach for deducing rms proton radii from charge-changing reactions of neutron-rich nuclei and the reaction-target dependence.

We report the charge-changing cross sections (σcc) of 24 p-shell nuclides on both hydrogen and carbon at about 900A MeV, of which 8,9Li, 10-12Be, 10,14,15B, 14,15,17-22N and 16O on hydrogen and 8,9Li on carbon are for the first time. Benefiting from the data set, we found a new and robust relationship between the scaling factor of the Glauber model calculations and the separation energies of the nuclei of interest on both targets. This allows us to deduce proton radii (Rp) for the first time from the cross sections on hydrogen. Nearly identical Rp values are deduced from both target data for the neutron-rich carbon isotopes; however, the Rp from the hydrogen target is systematically smaller in the neutron-rich nitrogen isotopes. This calls for further experimental and theoretical investigations.

Radioactive Beams for Image-Guided Particle Therapy: The BARB Experiment at GSI.

Several techniques are under development for image-guidance in particle therapy. Positron (ß+) emission tomography (PET) is in use since many years, because accelerated ions generate positron-emitting isotopes by nuclear fragmentation in the human body. In heavy ion therapy, a major part of the PET signals is produced by ß+-emitters generated via projectile fragmentation. A much higher intensity for the PET signal can be obtained using ß+-radioactive beams directly for treatment. This idea has always been hampered by the low intensity of the secondary beams, produced by fragmentation of the primary, stable beams. With the intensity upgrade of the SIS-18 synchrotron and the isotopic separation with the fragment separator FRS in the FAIR-phase-0 in Darmstadt, it is now possible to reach radioactive ion beams with sufficient intensity to treat a tumor in small animals. This was the motivation of the BARB (Biomedical Applications of Radioactive ion Beams) experiment that is ongoing at GSI in Darmstadt. This paper will present the plans and instruments developed by the BARB collaboration for testing the use of radioactive beams in cancer therapy.