Unveiling Novel Arginase Inhibitors for Cutaneous Leishmaniasis Using Drug Repurposing and Virtual Screening Approaches.

Leishmaniasis is a neglected tropical disease with a significant global health burden, particularly in developing countries, where it accounts for approximately 1.6 million new infections annually. Current therapeutic options are limited by severe adverse effects, toxicity, and drug resistance, highlighting the urgent need for novel treatment strategies.

Statine-based peptidomimetics as SARS-CoV-2 Papain-like protease inhibitors: in Silico and in vitro studies.

We investigated statin-based peptidomimetic compounds as inhibitors of SARS-CoV-2 papain-like protease (PLpro) by in silico methods, including molecular docking/dynamic simulations and ADMET prediction, as well as enzymatic in vitro assays. Five compounds (LQMed 426, 428, 430, 431, and 432) were identified as having promising interactions with the active site and an allosteric site of PLpro. The docking poses in the active site revealed that the compounds interacted with the catalytic triad (Cys111, His272, and Asp286).

In Vitro and In Silico Assessments of Curcuminoids and Turmerones from as Novel Inhibitors of Arginase.

: The anti- potential of and its derivatives, such as curcuminoids, is well-established, yet their mechanisms of action remain underexplored. This study investigates the inhibitory effects of extracts and curcumin on arginase, a key enzyme in polyamine and trypanothione biosynthesis, and evaluates their antiparasitic activity. : Extracts were prepared via rhizome successive maceration with hexane (HEXCURC), dichloromethane (DCCURC), and ethanol (ETOHCURC) and chemically characterized by a combination of chromatographic and spectrometric methods.

Molecular Modeling and Evaluation of Thioureas and Arylthioureas as Urease Inhibitors.

Ureases are metalloenzymes found in plants, algae, fungi, and bacteria that are responsible for hydrolyzing urea into carbamate and ammonia. The bacterium Helicobacter pylori, which is associated with gastrointestinal disorders, produces large amounts of urease to neutralize stomach acidity. The rising antibiotic resistance of H.

Molluscicidal and Schistosomicidal Activities of 2-(1-Pyrazol-1-)-1,3,4-thiadiazole Derivatives.

Schistosomiasis is caused by flatworms of the genus , for which mollusks of the genus are intermediate hosts. Niclosamide (NCL) is a molluscicide recommended by the World Health Organization (WHO) for control of . Although effective, it is expensive and environmentally toxic, which raises concerns regarding its widespread use.

XGBMUT: Predicting the Functional Impact of Missense Mutations Using an Extreme Gradient Boost Classifier.

Millions of new mutations have been discovered largely due to advancements in genome projects, but characterizing their effects through traditional wet-lab experiments remains labor-intensive and time-consuming. Functional prediction algorithms offer a solution by enabling the efficient screening of mutations, thereby saving time and resources. The objective of this study was to develop a competitive algorithm for predicting the functional impact of missense mutations.

In silico evaluation of N-aryl-1,10-phenanthroline-2-amines as potential inhibitors of T. cruzi GP63 zinc-metalloprotease by docking and molecular dynamics simulations.

Based on the in vitro trypanocidal efficacy of previously synthesized N-aryl-1,10-phenanthroline-2-amines (Phen1-20) (aryl = R-phenyl, 1- or 2-naphthyl), we explored the potential interactions of these derivatives as ligands of our comparative model of T. cruzi GP63 (TcGP63). This surface metalloprotease plays a crucial role in parasite adhesion to host cells and aids in cell invasion during T.

Synthesis and Structure-Activity Relationship of Thiourea Derivatives Against .

Leishmaniasis, caused by protozoa and transmitted by vectors, presents varied clinical manifestations based on parasite species and host immunity. The lack of effective vaccines or treatments has prompted research into new therapies, including thiourea derivatives, which have demonstrated antiprotozoal activities. We synthesized two series of ,'-disubstituted thiourea derivatives through the reaction of isothiocyanates with amines.

In vitro assays identified thiohydantoins with anti-trypanosomatid activity and molecular modelling studies indicated possible selective CYP51 inhibition.

This work investigates the anti-trypanosomal activities of ten thiohydantoin derivatives against the parasite Trypanosoma cruzi. Compounds with aliphatic chains (THD1, THD3, and THD5) exhibited the most promising IC against the epimastigote form of T. cruzi.

Effect of a thiohydantoin salt derived from l-Arginine on Leishmania amazonensis and infected cells: Insights from biological effects to molecular docking interactions.

Leishmaniasis is a neglected tropical disease caused by parasites of the genus Leishmania and is responsible for more than 1 million new cases and 70,000 deaths annually worldwide. Treatment has high costs, toxicity, complex and long administration time, several adverse effects, and drug-resistant strains, therefore new therapies are urgently needed. Synthetic compounds have been highlighted in the medicinal chemistry field as a strong option for drug development against different diseases.

Evaluation of Silybin Nanoparticles against Liver Damage in Murine Infection.

Silybin (SIB) is a hepatoprotective drug known for its poor oral bioavailability, attributed to its classification as a class IV drug with significant metabolism during the first-pass effect. This study explored the potential of solid lipid nanoparticles with (SLN-SIB-U) or without (SLN-SIB) ursodeoxycholic acid and polymeric nanoparticles (PN-SIB) as delivery systems for SIB. The efficacy of these nanosystems was assessed through in vitro studies using the GRX and Caco-2 cell lines for permeability and proliferation assays, respectively, as well as in vivo experiments employing a murine model of infection in BALB/c mice.

Statine-based peptidomimetic compounds as inhibitors for SARS-CoV-2 main protease (SARS-CoV‑2 Mpro).

COVID-19 is a multisystemic disease caused by the SARS-CoV-2 airborne virus, a member of the Coronaviridae family. It has a positive sense single-stranded RNA genome and encodes two non-structural proteins through viral cysteine-proteases processing. Blocking this step is crucial to control virus replication.

Novel naphthoquinone-1H-1,2,3-triazole hybrids: Design, synthesis and evaluation as inductors of ROS-mediated apoptosis in the MCF-7 cells.

The search for novel anticancer drugs is essential to expand treatment options, overcome drug resistance, reduce toxicity, promote innovation, and tackle the economic impact. The importance of these studies lies in their contribution to advancing cancer research and enhancing patient outcomes in the battle against cancer. Here, we developed new asymmetric hybrids containing two different naphthoquinones linked by a 1,2,3-1H-triazole nucleus, which are potential new drugs for cancer treatment.

-disubstituted Ureas as Novel Antiplatelet Agents: Synthesis, Pharmacological Evaluation and Studies.

Introduction: Thrombotic disorders are among the leading causes of morbidity and mortality worldwide. Drugs used in the prevention and treatment of atherothrombosis have pharmacokinetic limitations and adverse effects such as hemorrhagic conditions, highlighting the importance of developing more effective antiplatelet agents.

Methods: In this work, we synthesized -disubstituted ureas 3a-3j and evaluated their antiplatelet profiles through , , and studies.

Use of Methodologies to Predict the Bioavailability of Oral Suspensions: A Regulatory Approach.

Background: Oral suspensions are heterogeneous disperse systems, and the particle size distribution, crystalline form of the dispersed solid, and composition of the formulation can be listed as parameters that control the drug dissolution rate and its bioavailability.

Objective: The aim of this work was to develop a discriminative dissolution test, which, in association with in silico methodologies, can make it possible to safely anticipate bioavailability problems.

Methods: Nimesulide and ibuprofen (BCS class II) and cephalexin (BCS class I) oral suspensions were studied.

Molluscicidal and Cercaricidal Effects of Essential Oil Nanoemulsion.

Schistosomiasis is a tropical disease transmitted in an aqueous environment by cercariae from the genus. This disease affects 200 million people living in risk areas around the world. The control of schistosomiasis is realized by chemotherapy, wastewater sanitation, health education, and mollusk control using molluscicidal agents.

Physiologically based pharmacokinetic modelling of semaglutide in children and adolescents with healthy and obese body weights.

Aims: To develop paediatric physiologically based pharmacokinetic modelling (PBPK) models of semaglutide to estimate the pharmacokinetic profile for subcutaneous injections in children and adolescents with healthy and obese body weights.

Methods: Pharmacokinetic modelling and simulations of semaglutide subcutaneous injections were performed using the Transdermal Compartmental Absorption & Transit model implemented in GastroPlus v.9.

In silico and pharmacological study of N,S-acetal juglone derivatives as inhibitors of the P2X7 receptor-promoted in vitro and in vivo inflammatory response.

Purinergic receptors are transmembrane proteins responsive to extracellular nucleotides and are expressed by several cell types throughout the human body. Among all identified subtypes, the P2×7 receptor has emerged as a relevant target for the treatment of inflammatory disease. Several clinical trials have been conducted to evaluate the effectiveness of P2×7R antagonists.

Molluskicidal nanoemulsion of (DC.) N. Silveira for schistosomiasis control.

Schistosomiasis is caused by the parasite , which uses mollusks of the genus as intermediate hosts. In 2020, approximately 241 million people worldwide underwent treatment for schistosomiasis. For this reason, the World Health Organization encourages research on alternative molluskicides based on plant species.

Aryl Hydrocarbon Receptor as a Therapeutical Target of Environmentally Induced Skin Conditions.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, expressed in several tissues and involved in the response to environmental stressors. Studies have already associated exposure to environmental factors, such as organic air pollutants, products of the skin microbiota, and solar radiation, with the development/worsening of skin conditions, mediated by AhR. On the other hand, recent studies have shown that synthetic and natural compounds are able to modulate the activation of some AhR signaling pathways, minimizing the harmful response of these environmental stressors in the skin.

Synthesis, Biological Evaluation and Molecular Modeling Studies of Naphthoquinone Sulfonamides and Sulfonate Ester Derivatives as P2X7 Inhibitors.

ATP acts in the extracellular environment as an important signal, activating a family of receptors called purinergic receptors. In recent years, interest in the potential therapeutics of purinergic components, including agonists and antagonists of receptors, has increased. Currently, many observations have indicated that ATP acts as an important mediator of inflammatory responses and, when found in high concentrations in the extracellular space, is related to the activation of the P2X7 purinergic receptor.

Triazoles with inhibitory action on P2X7R impaired the acute inflammatory response in vivo and modulated the hemostatic balance in vitro and ex vivo.

Objective: The present study aimed to investigate five triazole compounds as P2X7R inhibitors and evaluate their ability to reduce acute inflammation in vivo.

Material: The synthetic compounds were labeled 5e, 8h, 9i, 11, and 12.

Treatment: We administered 500 ng/kg triazole analogs in vivo, (1-10 µM) in vitro, and 1000 mg/kg for toxicological assays.

Development of a validation protocol method for nucleic acid testing to detect human immunodeficiency virus, hepatitis C virus, and hepatitis B virus.

The concern about the risks of viral infections transmission through blood transfusion has led into a search for improvements on screening tests used for the selection of blood donors. Molecular biology techniques applied in researches of viral genomes, known as Nucleic Acid-amplification-Test (NAT), represent a technology capable of increasing transfusion safety by shortening the diagnostic window period. In Brazil, the implementation of this technology for the detection of HIV, HCV and HBV occurred due to the implantation of the NAT Kit - produced by Immunobiological Technology Institute (Biomanguinhos-FIOCRUZ), in the Brazilian blood centers.

Toxicological assessment of SGLT2 inhibitors metabolites using in silico approach.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the latest class of drugs approved to treat type 2 DM (T2DM). Although adverse effects are often caused by a metabolite rather than the drug itself, only the safety assessment of disproportionate drug metabolites is usually performed, which is of particular concern for drugs of chronic use, such as SGLT2i. Bearing this in mind, in silico tools are efficient strategies to reveal the risk assessment of metabolites, being endorsed by many regulatory agencies.

Alternative Methods for Pulmonary-Administered Drugs Metabolism: A Breath of Change.

Prediction of pulmonary metabolites following inhalation of a locally acting pulmonary drug is essential to the successful development of novel inhaled medicines. The lungs present metabolic enzymes, therefore they influence drug disposal and toxicity. The present review provides an overview of alternative methods to evaluate the pulmonary metabolism for the safety and efficacy of pulmonary delivery systems.