A5063500641- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Synthesis and Biological Evaluation
- Phenothiazines and Benzothiazines Synthesis and Activities
- Venomous Animal Envenomation and Studies
- Ion channel regulation and function
- Synthesis and biological activity
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Bioactive Compounds and Antitumor Agents
- Essential Oils and Antimicrobial Activity
- Meta-analysis and systematic reviews
- Organoselenium and organotellurium chemistry
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Force Microscopy Techniques and Applications
- Biochemical and Structural Characterization
Czech Academy of Sciences, Institute of Physics
2025
Universidade de São Paulo
2020-2024
Universidade Federal de São Carlos
2024
Instituto Internacional de Ecologia (Brazil)
2022
Instituto de Psicologia Comportamental de São Carlos
2020
Universidade Estadual Paulista (Unesp)
2003-2004
Chagas disease (CD), caused by the flagellate protozoan Trypanosoma cruzi, is a neglected tropical endemic in 21 countries. The only two antiparasitic drugs approved for its treatment, benznidazole and nifurtimox, have significant drawbacks. We present herein optimization of series substituted indoles that were identified through phenotypic screening against T. cruzi. Early lead compounds with balanced potency physicochemical properties advanced to animal studies but showed limited plasma...
Cruzain, the main cysteine protease of Trypanosoma cruzi, plays key roles in all stages parasite's life cycle, including nutrition acquisition, differentiation, evasion host immune system, and invasion cells. Thus, inhibition this validated target may lead to development novel drugs for treatment Chagas disease. In study, a multiparameter optimization (MPO) approach, molecular modeling, structure-activity relationships (SARs) were employed identification new benzimidazole derivatives as...
Leishmaniasis is a major infectious disease with hundreds of thousands new cases and over 20,000 deaths each year. The current drugs to treat this life-threatening infection have several drawbacks such as toxicity long treatment regimens. A library 1.8 million compounds, from which the hits reported here are publicly available, was screened against Leishmania infantum part an optimization program; compound found 2-aminobenzimidazole functionality presenting moderate potency, low metabolic...
Chagas disease is a neglected tropical caused by Trypanosoma cruzi. Because current treatments present several limitations, including long duration, variable efficacy and serious side effects, there an urgent need to explore new antitrypanosomal drugs. The study describes the hit-to-lead optimization of 2-aminobenzimidazole hit 1 identified through in vitro phenotypic screening chemical library against intracellular cruzi amastigotes, which focused on optimizing potency, selectivity,...
Background: Chagas disease is caused by the parasite Trypanosoma cruzi, and lack of effective safe treatments makes identifying new classes compounds with anti-T. cruzi activity paramount importance. Methods: Hit-to-lead exploration a metabolically stable N-imidazoylpiperazine was performed. Results: Compound 2, piperazine derivative active against T. selected to perform hit-to-lead exploration, which involved design, synthesis biological evaluation 39 derivatives. Conclusion: Compounds 6e...
A series of benzene sulphonamides with good potency and selectivity against Leishmania spp. intracellular amastigotes was identified by high-throughput screening. Approximately 200 compounds were synthesized as part a hit-to-lead optimization program. The the appears to be strongly dependent on lipophilicity, making identification suitable orally available candidates challenging due poor pharmacokinetics. Despite not identifying clinical candidate, likely solvent exposed area found, best...
Background: Schiff bases are synthetically accessible compounds that have been used in medicinal chemistry. Methods & results: In this work, 27 derived from diaminomaleonitrile were synthesized high yields (80-98%). Molecular docking studies suggested the interact with catalytic site of cruzain. The most active cruzain inhibitor, analog 13 (IC50 = 263 nM), was predicted to form an additional hydrophobic contact Met68 binding enzyme. A strong correlation between IC50 values and ChemScore...
Abstract An early exploration of the benzothiazole class against two kinetoplastid parasites, Leishmania infantum and Trypanosoma cruzi , has been performed after identification a derivative as suitable antileishmanial initial hit. The first series derivatives focused on acyl fragment its class, evaluating diverse linear cyclic, alkyl aromatic substituents, identified other potent compounds, phenyl cyclohexyl derivatives. Subsequently, new compounds were designed to assess impact presence...
This study introduces further insights from the hit-to-lead optimization process involving a series of benzimidazole derivatives acting as inhibitors cruzain enzyme, which targets Trypanosoma cruzi, causative parasite Chagas disease. Here, we present design, synthesis and biological evaluation 30 new compounds third generation analogues with trypanocidal activity, aiming to enhance our understanding their pharmacokinetic profiles establish structure-metabolism relationships within series....
Microorganisms can induce diseases with significant clinical implications for human health. Multidrug‐resistant microorganisms have been on the rise worldwide over past few decades, and no new antibiotics introduced to market in a considerable amount of time. Such situation highlights urgency discovering antimicrobial drugs address this pressing issue. Therefore, objective study was identify bioactive compounds against 15 species bacteria 5 fungi relevance through vitro screening 58...
Chagas disease is a neglected tropical caused by the parasite Trypanosoma cruzi, discovered over hundred years ago. With 75 million people at risk, lack of effective and safe treatments makes identifying new classes compounds with anti-Trypanosoma cruzi activity paramount importance. Herein, we report discovery, structure-activity relationships, hit-to-lead exploration metabolically stable N-imidazoylpiperazine. Inspired our previous studies carbamoyl imidazole series featuring cruzain...