Enzymatic Synthesis of Austroeupatol Esters with Enhanced Antiprotozoal Activity.

Austroeupatol, the principal diterpene isolated from the invasive shrub , holds promise for structural diversification and biological assessment of its derivatives due to its abundant availability and high yield isolation. We propose an efficient enzymatic synthesis of a series of austroeupatol esters derived from aliphatic and heterocyclic carboxylic acids. Systematic optimization of reaction parameters, including enzyme type and quantity, acylating agent amount, solvent, and temperature, was conducted.

In vitro antiviral activity of favipiravir and its 6- and 3-O-substituted derivatives against coronavirus: Acetylation leads to improvement of antiviral activity.

Favipiravir is currently approved for the treatment of the influenza virus and has shown encouraging results in terms of antiviral capacity in clinical studies against severe acute respiratory syndrome coronavirus 2. Favipiravir is a prodrug, where its favipiravir-ribofuranosyl-5B-triphosphate metabolite is capable of blocking RNA replication of the virus. However, the antiviral efficiency of favipiravir is limited by two factors: (i) low accumulation in plasma and rapid excretion/elimination post-administration and (ii) low conversion rate into the active metabolite.

Tautomerism and Rotamerism of Favipiravir and Halogenated Analogues in Solution and in the Solid State.

Favipiravir is an important selective antiviral against RNA-based viruses, and currently, it is being repurposed as a potential drug for the treatment of COVID-19. This type of chemical system presents different carboxamide-rotameric and hydroxyl-tautomeric states, which could be essential for interpreting its selective antiviral activity. Herein, the tautomeric 3-hydroxypyrazine/3-pyrazinone pair of favipiravir and its 6-substituted analogues, 6-Cl, 6-Br, 6-I, and 6-H, were fully investigated in solution and in the solid state through ultraviolet-visible, H nuclear magnetic resonance, infrared spectroscopy, and X-ray diffraction techniques.

One-step synthesis of favipiravir from Selectfluor® and 3-hydroxy-2-pyrazinecarboxamide in an ionic liquid.

Favipiravir is an important selective antiviral that emerged as an alternative against COVID-19 during the pandemic. Its synthesis has gained great interest and the conventional strategies proceed through multiple-step protocols (6-7 reaction steps), which involve, in addition, several drawbacks with global yields, lower than 34%. Herein, a simple, economical, eco-friendly and scalable (1 g) one-step protocol for the synthesis of favipiravir from the direct fluorination of the available 3-hydroxy-2-pyrazinecarboxamide with Selectfluor® is reported.

Anti- Properties of Sesquiterpene Lactones Isolated from spp.: In Vitro and In Silico Studies.

species (Asteraceae) have been a rich source of terpenoid compounds, mainly sesquiterpene lactones, several of which show antiprotozoal activity. In the search for new trypanocidal compounds, var. and were studied.

Preclinical Studies and Drug Combination of Low-Cost Molecules for Chagas Disease.

Chagas disease is caused by the protozoan (). It remains the major parasitic disease in Latin America and is spreading worldwide, affecting over 10 million people. Hundreds of new compounds with trypanosomicidal action have been identified from different sources such as synthetic or natural molecules, but they have been deficient in several stages of drug development (toxicology, scaling-up, and pharmacokinetics).

Phenotypic and Target-Directed Screening Yields New Acaricidal Alternatives for the Control of Ticks.

, the "common cattle tick", is the most important ectoparasite in livestock worldwide due to the economic and health losses it produces. This tick is a vector for pathogens of several tick-borne diseases. In Latin American countries, damages reach approximately USD 500 million annually due to tick infections, as well as tick-borne diseases.

Identification of 2-(4-N,N-Dimethylaminophenyl)-5-methyl-1-phenethyl-1H-benzimidazole targeting HIV-1 CA capsid protein and inhibiting HIV-1 replication in cellulo.

The capsid (CA) subunit of the HIV-1 Gag polyprotein is involved in several steps of the viral cycle, from the assembly of new viral particles to the protection of the viral genome until it enters into the nucleus of newly infected cells. As such, it represents an interesting therapeutic target to tackle HIV infection. In this study, we screened hundreds of compounds with a low cost of synthesis for their ability to interfere with Gag assembly in vitro.

Novel tick glutathione transferase inhibitors as promising acaricidal compounds.

Ticks are important ectoparasites with a worldwide distribution. The most commonly used method for tick control involves the use of acaricides. The main problem is that its indiscriminate use has led to the selection of resistant tick populations.

Quick Spreading of Populations of an Exotic Firefly throughout Spain and Their Recent Arrival in the French Pyrenees.

In August 2018, a firefly () of American origin was observed in several localities in Girona (Catalonia, Spain) and was described as by Zaragoza-Caballero and Vinolas, 2018. Here, we show that this species dispersed very quickly throughout northeastern Spain and was, in 2020, observed in the French Pyrenees. The animal's quick progress is documented, and part of its biology is described (dispersion speed, land use, phenology, identification of all life stages).

A phenomenological-based model of the endometrial growth and shedding during the menstrual cycle.

The human endometrium presents a remarkable growth dynamic with an outstanding regenerative capacity. This work aims to develop a phenomenological-based dynamic model to predict the volume changes in the functional layer of the endometrium in each phase of the menstrual cycle. This model considers changes in the endometrial tissue, the blood flow through the spiral arteries, the shedding of the endometrial cells, and the menstrual blood flow.

Preclinical Studies in Anti- Drug Development.

The trypanosomatid parasites , and are the causative agents of human African trypanosomiasis, Chagas Disease and Leishmaniasis, respectively. These infections primarily affect poor, rural communities in the developing world, and are responsible for trapping sufferers and their families in a disease/poverty cycle. The development of new chemotherapies is a priority given that existing drug treatments are problematic.

Identification of a Potential Inhibitor of the FIV p24 Capsid Protein and Characterization of Its Binding Site.

Feline immunodeficiency virus (FIV) is a veterinary infective agent for which there is currently no efficient drug available. Drugs targeting the lentivirus capsid are currently under development for the treatment of human immunodeficiency virus 1 (HIV-1). Here we describe a lead compound that interacts with the FIV capsid.

Pyrazol(in)e derivatives of curcumin analogs as a new class of anti- agents.

We report the synthesis and biological evaluation of a small library of 15 functionalized 3-styryl-2-pyrazolines and pyrazoles, derived from curcuminoids, as trypanosomicidal agents. The compounds were prepared via a cyclization reaction between the corresponding curcuminoids and the appropriate hydrazines. All of the derivatives synthesized were investigated for their trypanosomicidal activities.

Antiprotozoal Compounds from (Asteraceae).

The dewaxed dichloromethane extract of and the compounds isolated from it were tested for their activity on epimastigotes and promastigotes. The extract of showed activity against both parasites with IC values of 7 g/mL and 31 g/mL, respectively. Fractionation of the dichloromethane extract led to the isolation of euparin, jaceidin, santhemoidin C, and eucannabinolide.

Why Does a Growth Mindset Intervention Impact Achievement Differently across Secondary Schools? Unpacking the Causal Mediation Mechanism from a National Multisite Randomized Experiment.

The growth mindset or the belief that intelligence is malleable has garnered significant attention for its positive association with academic success. Several recent randomized trials, including the National Study of Learning Mindsets (NSLM), have been conducted to understand why, for whom, and under what contexts a growth mindset intervention can promote beneficial achievement outcomes during critical educational transitions. Prior research suggests that the NSLM intervention was particularly effective in improving low-achieving 9th graders' GPA, while the impact varied across schools.

Drug Targets: Screening for Small Molecules that Inhibit Fasciola hepatica Enzymes.

The in vitro screening of small molecules for enzymatic inhibition provides an efficient means of finding new compounds for developing drug candidates. This strategy has the advantage of being rapid and inexpensive to perform. Enzymes are suitable targets for screening when simple methods to obtain them and measure their activities are available and there is evidence of their essential role in the parasite's life cycle.

Novel and selective inactivators of Triosephosphate isomerase with anti-trematode activity.

Trematode infections such as schistosomiasis and fascioliasis cause significant morbidity in an estimated 250 million people worldwide and the associated agricultural losses are estimated at more than US$ 6 billion per year. Current chemotherapy is limited. Triosephosphate isomerase (TIM), an enzyme of the glycolytic pathway, has emerged as a useful drug target in many parasites, including Fasciola hepatica TIM (FhTIM).

A Nature-Inspired Design Yields a New Class of Steroids Against Trypanosomatids.

Chagas disease and Leishmaniasis are neglected endemic protozoan diseases recognized as public health problems by the World Health Organization. These diseases affect millions of people around the world however, efficient and low-cost treatments are not available. Different steroid molecules with antimicrobial and antiparasitic activity were isolated from diverse organisms (ticks, plants, fungi).

Infrared-Based Motility Assay Identified New Hits for Nematicide Drug Development.

Nematode parasites have a profound impact on humankind, infecting nearly one-quarter of the world's population, as well as livestock. There is a pressing need for discovering nematicides due to the spread of resistance to currently used drugs. The free-living nematode is a formidable experimentally tractable model organism that offers key advantages in accelerating nematicide discovery.

Novel and Selective Triosephosphate Isomerase Inhibitors with Acaricidal Activity.

The cattle tick is one of the most important ectoparasites causing significant economic losses for the cattle industry. The major tool of control is reducing the number of ticks, applying acaricides in cattle. However, overuse has led to selection of resistant populations of to most of these products, some even to more than one active principle.

Isolation and Structural Characterization of Bioactive Molecules on Prostate Cancer from Mayan Traditional Medicinal Plants.

Prostate cancer is the most common cancer in men around the world. It is a complex and heterogeneous disease in which androgens and their receptors play a crucial role in the progression and development. The current treatment for prostate cancer is a combination of surgery, hormone therapy, radiation and chemotherapy.

Short term comparison between blind and ultrasound guided injection in morton neuroma.

Objective: The aim of this work is to compare the effectiveness of blind and ultrasound-guided injection for Morton's neuroma (MN) to determine which is more appropriate as the initial procedure in conservative treatment.

Methods: This is an evaluator-blinded randomised trial. Of the 56 included patients, 27 were assigned to the blind group (A) and 29 to the ultrasound-guided group (B).