Structure-activity relationships of novel -imidazoylpiperazines with potent anti- activity.

Chagas disease is caused by the parasite , and the lack of effective and safe treatments makes identifying new classes of compounds with anti- activity of paramount importance. Hit-to-lead exploration of a metabolically stable -imidazoylpiperazine was performed. Compound , a piperazine derivative active against , was selected to perform the hit-to-lead exploration, which involved the design, synthesis and biological evaluation of 39 new derivatives.

Multiparameter Optimization of Trypanocidal Cruzain Inhibitors With Activity and Favorable Pharmacokinetics.

Cruzain, the main cysteine protease of , plays key roles in all stages of the parasite's life cycle, including nutrition acquisition, differentiation, evasion of the host immune system, and invasion of host cells. Thus, inhibition of this validated target may lead to the development of novel drugs for the treatment of Chagas disease. In this study, a multiparameter optimization (MPO) approach, molecular modeling, and structure-activity relationships (SARs) were employed for the identification of new benzimidazole derivatives as potent competitive inhibitors of cruzain with trypanocidal activity and suitable pharmacokinetics.

Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling Studies.

Cyclooxygenase (COX) and lipoxygenase (LOX) are key targets for the development of new anti-inflammatory agents. LOX, which is involved in the biosynthesis of mediators in inflammation and allergic reactions, was selected for a biochemical screening campaign to identify LOX inhibitors by employing the main natural product library of Brazilian biodiversity. Two prenyl chalcones were identified as potent inhibitors of LOX-1 in the screening.

Chalcones and their B-aryl analogues as myeloperoxidase inhibitors: In silico, in vitro and ex vivo investigations.

In the present study, a series of chalcones and their B-aryl analogues were prepared and evaluate as inhibitors of myeloperoxidase (MPO) chlorinating activity, using in vitro and ex vivo assays. Among these, B-thiophenyl chalcone (analogue 9) demonstrated inhibition of in vitro and ex vivo MPO chlorinating activity, exhibiting IC value of 0.53 and 19.

USPHS Corps Care : Force Health Protection for Public Health Officers During the Ebola and COVID-19 Responses.

Force health protection (FHP) is defined as "the prevention of disease and injury in order to protect the strength and capabilities" of any service population. FHP was the foundational principal of the US Public Health Service (USPHS). President John Adams' signing of An Act for Sick and Disabled Seamen on July 16, 1798, marked the first dedication of US federal resources to ensuring the well-being of US civilian sailors and Naval service members.