Expanding the antiprotozoal activity and the mechanism of action of n-butyl and iso-butyl ester of quinoxaline-1,4-di--oxide derivatives against , , and An and approach.

In this study, n-butyl and iso-butyl quinoxaline-7-carboxylate-1,4-di--oxide derivatives were evaluated against () (), and (). The potential mechanism of action determination was approached by analysis on and triosephosphate isomerase (TIM and TIM, respectively), and on thioredoxin reductase (). Enzyme inactivation assays were performed on recombinant GTIM and TrxR.

Biological Evaluations and Computer-Aided Approaches of Janus Kinases 2 and 3 Inhibitors for Cancer Treatment: A Review.

Cancer remains one of the leading diseases of mortality worldwide. Janus kinases 2/3 (JAK2/3) have been considered a drug target for the development of drugs to treat different types of cancer. JAK2/3 play a critical role in innate immunity, inflammation, and hematopoiesis by mediating the signaling of numerous cytokines, growth factors, and interferons.

Expanding the chemical space of ester of quinoxaline-7-carboxylate 1,4-di--oxide derivatives as potential antitubercular agents.

Tuberculosis is a worldwide health problem that warrants attention given that the current treatment options require a long-term chemotherapeutic period and have reported the development of () multidrug resistant strains. In this study, -butyl and isobutyl quinoxaline-7-carboxylate 1,4-di--oxide were evaluated against replicating and non-replicating H37Rv strains. The results showed that seventeen of the twenty-eight derivatives have minimum inhibitory concentration (MIC) values lower than isoniazid (2.

Design, Synthesis, and In Vitro and In Silico Evaluation of 1,3,4-Oxadiazoles as Anti-Trypanosoma cruzi and Anti-Leishmania mexicana Agents.

A series of novel 4-acetyl-1,3,4-oxadiazole derivatives was designed and synthesized for their biological evaluation in vitro against Trypanosoma cruzi (T. cruzi) and Leishmania mexicana (L. mexicana).

A Computational Approach Using α-Carbonic Anhydrase to Find Anti-Trypanosoma cruzi Agents.

Background: Chagas disease has an ineffective drug treatment despite efforts made over the last four decades. The carbonic anhydrase of Trypanosoma cruzi (α-TcCA) has emerged as an interesting target for the design of new antiparasitic compounds due to its crucial role in parasite processes.

Objective: The aim of this study was to identify potential α-TcCA inhibitors with trypanocide activity.

Triose Phosphate Isomerase Structure-Based Virtual Screening and In Vitro Biological Activity of Natural Products as Inhibitors.

Cutaneous leishmaniasis (CL) is a public health problem affecting more than 98 countries worldwide. No vaccine is available to prevent the disease, and available medical treatments cause serious side effects. Additionally, treatment failure and parasite resistance have made the development of new drugs against CL necessary.

Ligand-Based and Structure-Based Virtual Screening of New Sodium Glucose Cotransporter Type 2 Inhibitors.

Background: Diabetes mellitus is a metabolic disease that causes multiple complications and common comorbidities, which decreases the quality of life for people affected by the disease. Sodium glucose cotransporter type 2 (SGLT2) participates in the reabsorption of 90% of glucose in the kidneys; therefore, it is an attractive drug target for controlling blood glucose levels.

Objective: The aim in this work was to obtain new potential SGLT2 inhibitors.

Phenothiazine-based virtual screening, molecular docking, and molecular dynamics of new trypanothione reductase inhibitors of Trypanosoma cruzi.

Phenothiazine derivatives can unselectively inhibit the trypanothione-dependent antioxidant system enzyme trypanothione reductase (TR). A virtual screening of 2163 phenothiazine derivatives from the ZINC15 and PubChem databases docked on the active site of T. cruzi TR showed that 285 compounds have higher affinity than the natural ligand trypanothione disulfide.

Molecular docking and dynamic simulations of quinoxaline 1,4-di-N-oxide as inhibitors for targets from Trypanosoma cruzi, Trichomonas vaginalis, and Fasciola hepatica.

Context: Quinoxaline 1,4-di-N-oxide is a scaffold with a wide array of biological activities, particularly its use to develop new antiparasitic agents. Recently, these compounds have been described as trypanothione reductase (TR), triosephosphate isomerase (TIM), and cathepsin-L (CatL) inhibitors from Trypanosoma cruzi, Trichomonas vaginalis, and Fasciola hepatica, respectively.

Methods: Therefore, the main objective of this work was to analyze quinoxaline 1,4-di-N-oxide derivatives of two databases (ZINC15 and PubChem) and literature by molecular docking, dynamic simulation and complemented by MMPBSA, and contact analysis of molecular dynamics' trajectory on the active site of the enzymes to know their potential effect inhibitory.

Advances in Protozoan Epigenetic Targets and Their Inhibitors for the Development of New Potential Drugs.

Protozoan parasite diseases cause significant mortality and morbidity worldwide. Factors such as climate change, extreme poverty, migration, and a lack of life opportunities lead to the propagation of diseases classified as tropical or non-endemic. Although there are several drugs to combat parasitic diseases, strains resistant to routinely used drugs have been reported.

Virtual Screening of Benzimidazole Derivatives as Potential Triose Phosphate Isomerase Inhibitors with Biological Activity against .

() is a causal agent of cutaneous leishmaniasis (CL), a "", for which the search for new drugs is a priority. Benzimidazole is a scaffold used to develop antiparasitic drugs; therefore, it is interesting molecule against . In this work, a ligand-based virtual screening (LBVS) of the ZINC15 database was performed.

Ligand-Based Virtual Screening and Molecular Docking of Benzimidazoles as Potential Inhibitors of Triosephosphate Isomerase Identified New Trypanocidal Agents.

() is a parasite that affects humans and other mammals. depends on glycolysis as a source of adenosine triphosphate (ATP) supply, and triosephosphate isomerase (TIM) plays a key role in this metabolic pathway. This enzyme is an attractive target for the design of new trypanocidal drugs.

Analysis of Potential Drug Targets for Protozoan Infections.

Background: Currently, protozoan infectious diseases affect billions of people every year. Their pharmacological treatments offer few alternatives and are restrictive due to undesirable side effects and parasite drug resistance.

Objective: In this work, three ontology-based approaches were used to identify shared potential drug targets in five species of protozoa.

Ligand-based virtual screening, molecular docking, and molecular dynamics of eugenol analogs as potential acetylcholinesterase inhibitors with biological activity against Spodoptera frugiperda.

The development of new, more selective, environmental-friendly insecticide alternatives is in high demand for the control of Spodoptera frugiperda (S. frugiperda). The major objective of this work was to search for new potential S.

Natural and Synthetic Naphthoquinones as Potential Anti-Infective Agents.

Background: Naphthoquinones are a class of aromatic compounds relevant for their chemical characteristics, structural properties, and biological activity. These compounds are found in nature with a wide range of effects, highlighting their antibacterial, antifungal, and antiprotozoal properties. Additionally, naphthoquinones are used as a scaffold to obtain new derivatives with pharmacological potential, mainly compounds against parasitic diseases.