Novel indole-based marinoquinolines as promising candidates against Toxoplasma gondii.

Toxoplasma gondii, an obligate intracellular parasite, infects approximately one-third of the global population, making toxoplasmosis a significant public health concern. The current treatment - typically a combination of pyrimethamine and sulfadiazine - is limited to the acute phase of infection, and it often causes allergic reactions and severe side effects. Marinoquinolines (MQs), a class of compounds originally isolated from marine microorganisms, have exhibited promising pharmacological properties including anti-T.

ADME Properties in Drug Delivery.

In recent decades, the identification of thousands of lead compounds, through development of analytical, synthetic, and computational techniques has occurred [...

Multiple targets directed screening of compounds from northeastern Brazilian fruits with activity in oxidative stress pathways associated with vascular damage throughout ageing.

Advancing age is a predominant risk factor for several important human pathologies, including cardiovascular diseases. The fruits L., Linn.

Exploring Lamiaceae diterpenoids as potential multitarget therapeutics for leishmaniasis and chagas disease.

Neglected tropical diseases such as Leishmaniasis and Chagas disease remain critical public health challenges. This study applied ligand-based virtual screening to a dataset of 4,150 secondary metabolites from the Lamiaceae family, aiming to identify multitarget molecules against four Leishmania species (L. infantum, L.

AmIActive (AIA): A Large-scale QSAR Based Target Fishing and Polypharmacology Predictive Web Tool.

Here, we introduce AmIActive (AIA), a QSAR-based web tool for biological activity prediction and target fishing. The AIA system uses QSAR models trained with biological activity data from the ChEMBL database and currently covers single proteins, protein complexes, protein families, cell lines, organisms, and tissues. The system contains 3,239 models corresponding to 2,277 distinct targets of interest.

Targets Involved in the Pharmacology of Bothrops Snakebite: and Future Perspectives.

Despite their hazardous nature, snake venoms hold immense potential for the development of novel therapies. This summary delves into the key aspects of snake venom research, focusing on their significance as targets for neutralization, their utility as novel drugs, the application of in silico studies, and future prospects with nanotechnology. Significance of Snake Venom: Snake venom harbors a rich diversity of toxic proteins with a wide range of biological activities.

Repeated-Dose Toxicity of Lauric Acid and Its Preventive Effect Against Tracheal Hyper-Responsiveness in Wistar Rats with Possible Molecular Targets.

Background/objectives: Lauric acid (LA), a medium-chain fatty acid, is a promising drug for asthma treatment. This study evaluated the toxicity of repeated doses and the effect of LA on pulmonary ventilation and tracheal reactivity in asthmatic Wistar rats and identified possible molecular targets of LA action .

Methods: The rats were divided into control (CG) and LA-treated groups at 100 mg/kg (AL100G) for toxicity analysis.

2-Aminothiophene Derivatives-New Drug Candidates Against Leishmaniasis: Drug Design, Synthesis, Pharmacomodulation, and Antileishmanial Activity.

: Leishmaniasis is one of the 20 Neglected Tropical Diseases according to the WHO, affecting approximately 12 million people in four continents, generating serious public health problems. The lack of therapeutic options, associated with toxicity and the emergence of resistance to the few available drugs, makes it urgent to develop new drug options. In this context, the aims of this work are to expand the knowledge about the pharmacophore group responsible for the antileishmanial potential of 2-aminothiophene derivatives.

Guanidines Conjugated with Cell-Penetrating Peptides: A New Approach for the Development of Antileishmanial Molecules.

Leishmaniasis is a neglected tropical disease caused by a protozoan of the genus Leishmania, which has visceral and cutaneous forms. The symptoms of leishmaniasis include high fever and weakness, and the cutaneous infection also causes lesions under the skin. The drugs used to treat leishmaniasis have become less effective due to the resistance mechanisms of the protozoa.

Predicting the Anti-SARS-CoV-2 Potential of Isoquinoline Alkaloids from Brazilian Siparunaceae Species Using Chemometric Tools.

The COVID-19 pandemic has caused over 7 million deaths globally in the past four years. spp. (Siparunaceae), which is used in Brazilian folk medicine, is considered a genus with potential antiviral alternatives.

Dolichocarpols G-X: Previously undescribed macrocyclic humulene sesquiterpenoids from Anaxagorea dolichocarpa.

Eleven previously undescribed macrocyclic humulene sesquiterpenoids, dolichocarpols G-Q (1-11), five undescribed bicyclic, dolichocarpols R-V (12-16) and two undescribed norsesquiterpenes, dolichocarpols W-X (17-18) were isolated from the roots of Anaxagorea dolichocarpa. Their structures were unequivocally determined by the analysis of NMR, HRESIMS, and IR data, along with NMR and ECD quantum-mechanical calculations, followed by the application of the DP4+ method. Most compounds possess an ether bridge between different carbons, whereas compounds 13/14 and 15/16 are diastereomers isomerized at C-7/C-10 and at C-7/C-10/C-12, respectively.

Structure-based Virtual Screening and Drug Design Development of Leishmanicidal Pyrimidines.

Leishmaniasis is a neglected disease caused by parasites of the genus Leishmania sp. that causes approximately 1 million cases and 650,000 deaths annually worldwide. Its treatment has several limitations mainly due to high toxicity and clinical resistance, and the search for alternatives is highly desirable.

AMTAC-19, a Spiro-Acridine Compound, Induces In Vitro Antitumor Effect via the ROS-ERK/JNK Signaling Pathway.

Colorectal cancer remains a significant cause of mortality worldwide. A spiro-acridine derivative, ()-1'-((4-bromobenzylidene)amino)-5'-oxo-1',5'-dihydro-10-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-19), showed significant cytotoxicity in HCT-116 colorectal carcinoma cells (half maximal inhibitory concentration, IC50 = 10.35 ± 1.

MuDRA-Based Virtual Screening of Terpenes for Anti-Leishmania Infantum Activity: In Vitro Validation and Mechanistic Insights from Molecular Docking.

Leishmaniasis, caused by Leishmania parasites, presents a major global health challenge due to limitations of existing treatments, including toxicity, side effects, drug resistance, and high costs. This study utilized the MuDRA (Multi-Descriptor Read Across) model for virtual screening to identify potential anti-Leishmania infantum compounds. A set of 15 terpenes and steroids was screened, leading to the identification of four promising candidates-lupeol, xylodiol, morolic acid, and trachyloban-18-oic acid.

MolPredictX: A Pioneer Mobile App Version for Online Biological Activity Predictions by Machine Learning Models.

MolPredictX is a free-access web tool in which it is possible to analyze the prediction of biological activity of chemical molecules. MolPredictX has been available online to the general public for just over a year and has now gone through its first update. We also developed its version for android, being the first free app capable of predicting biological activities.

and evaluation of the anti-leishmania activity of synthetic chalcones.

Leishmaniasis is a group of neglected, vector-borne infectious diseases that affect millions of people around the world. The medications available for its treatment, especially in cases of visceral leishmaniasis, are old, outdated and have serious side effects. In this work, 10 chalcones were synthesised and evaluated against promastigotes and axenic amastigotes of .

Synergistic effect of new pyrimidine derivative with oxacilin against methicillin-resistant .

This work aimed to synthesize a new pyrimidine with potential application against antimicrobial resistance. was synthesized through condensation reaction between and . The antimicrobial evaluation was carried out using the microdilution method in Mueller-Hinton Agar and predictions using different software.

3D-QSAR, Pharmacophore Modeling, ADMET and DFT Studies of Halogenated Conjugated Dienones as Potent MAO-B Inhibitors.

Introduction: It has been reported that the extension of conjugation in chalcone scaffolds considerably enhanced the potency, selectivity, reversibility, and competitive mode of MAO-B inhibition. In this study, using the experimental results of IC50 values of fifteen halogenated conjugated dienone derivatives (MK1-MK15) against MAO-B, we developed a 3DQSAR model.

Methods: Further, we created a 3D pharmacophore model in active compounds in the series.

In Silico and In Vitro Studies of Terpenes from the Fabaceae Family Using the Phenotypic Screening Model against the SARS-CoV-2 Virus.

In 2019, the emergence of the seventh known coronavirus to cause severe illness in humans triggered a global effort towards the development of new drugs and vaccines for the SARS-CoV-2 virus. These efforts are still ongoing in 2024, including the present work where we conducted a ligand-based virtual screening of terpenes with potential anti-SARS-CoV-2 activity. We constructed a Quantitative Structure-Activity Relationship (QSAR) model from compounds with known activity against SARS-CoV-2 with a model accuracy of 0.

Multitarget Compounds for Neglected Diseases: A Review.

Neglected diseases are a group of infectious diseases, many of them parasitic, that mainly affect the poorest populations with limited access to health services, especially those living in remote rural areas and slums. According to the World Health Organization (WHO), neglected diseases put the lives of more than 200 million people at risk, and treatment is made difficult by the occurrence of resistance to existing medications, as well as the high level of toxicity. In this way, the potential of multitarget compounds is highlighted, defined as compounds designed to modulate multiple targets of relevance to disease, with the overall goal of enhancing efficacy and/or improving safety.

In Silico and In Vitro Evaluation of the Antifungal Activity of a New Chromone Derivative against spp.

species are frequently implicated in the development of both superficial and invasive fungal infections, which can impact vital organs. In the quest for novel strategies to combat fungal infections, there has been growing interest in exploring synthetic and semi-synthetic products, particularly chromone derivatives, renowned for their antimicrobial properties. In the analysis of the antifungal activity of the compound ()-benzylidene-chroman-4-one against , in silico and laboratory tests were performed to predict possible mechanisms of action pathways, and in vitro tests were performed to determine antifungal activity (MIC and MFC), to verify potential modes of action on the fungal cell membrane and wall, and to assess cytotoxicity in human keratinocytes.

Multi-target Phenylpropanoids Against Epilepsy.

Epilepsy is a neurological disease with no defined cause, characterized by recurrent epileptic seizures. These occur due to the dysregulation of excitatory and inhibitory neurotransmitters in the central nervous system (CNS). Psychopharmaceuticals have undesirable side effects; many patients require more than one pharmacotherapy to control crises.

Inhibition of the morphological transition of Candida spp. by riparins I-IV.

Candida spp. is an opportunistic pathogen capable of causing superficial to invasive infections. Morphological transition is one of the main virulence factors of this genus and, therefore, is an important variable to be considered in pharmacological interventions.

Myrtucommulones and Related Acylphloroglucinols from Myrtaceae as a Promising Source of Multitarget SARS-CoV-2 Cycle Inhibitors.

The LABEXTRACT plant extract bank, featuring diverse members of the Myrtaceae family from Brazilian hot spot regions, provides a promising avenue for bioprospection. Given the pivotal roles of the Spike protein and 3CL and PL proteases in SARS-CoV-2 infection, this study delves into the correlations between the Myrtaceae species from the Atlantic Forest and these targets, as well as an antiviral activity through both and analyses. The results uncovered notable inhibitory effects, with and standing out, while proved to be multitarget, presenting inhibition values above 72% in the three targets analyzed.