2-Amino-thiophene derivatives present antileishmanial activity mediated by apoptosis and immunomodulation in vitro.

This study evaluated the effects of 2-amino-thiophene derivatives on the promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and their possible mechanisms of action. Initially, we evaluated the antileishmanial activity of ten 2-amino-thiophene derivatives on promastigote and axenic amastigote forms of Leishmania amazonensis and their cytotoxicity against murine macrophages and human red blood cells. Three promising compounds were selected for studies of the cell death process using flow cytometry analysis and a DNA fragmentation assay.

Docking Studies for Multi-Target Drugs.

The most basic principle of drug action is found in the lock and key model, where the highest possible affinity for a target that also avoids side effects is desired. For many years this was understood as being "one drug, for one target, for one disease", however researchers began to observe that certain diseases are best treated with multi-target drugs. In recent years, studies have sought out polypharmacological compounds acting on multiple targets against complex (multifactorial) diseases, such as cancer, neurodegenerative disease, and certain infections.

Artificial Neural Network Methods Applied to Drug Discovery for Neglected Diseases.

Among the chemometric tools used in rational drug design, we find artificial neural network methods (ANNs), a statistical learning algorithm similar to the human brain, to be quite powerful. Some ANN applications use biological and molecular data of the training series that are inserted to ensure the machine learning, and to generate robust and predictive models. In drug discovery, researchers use this methodology, looking to find new chemotherapeutic agents for various diseases.

Computational and Investigative Study of Flavonoids Active Against Typanosoma cruzi and Leishmania spp.

Flavonoid compounds active against Trypanosoma cruzi and Leishmania species were submitted to several methodologies in silico: docking with the enzymes cruzain and trypanothione reductase (from T. cruzi), and N-myristoyltransferase, dihydroorotate dehydrogenase, and trypanothiona reductase (from Leishmania spp). Molecular maps of the complexes and the ligands were calculated.

Computer Aided Drug Design Studies in the Discovery of Secondary Metabolites Targeted Against Age-Related Neurodegenerative Diseases.

Secondary metabolites are plant products that occur usually in differentiated cells, generally not being necessary for the cells themselves, but likely useful for the plant as a whole. Neurodegeneration can be found in many different levels in the neurons, it always begins at the molecular level and progresses toward the systemic levels. Usually, alterations are observed such as decreasing cholinergic impulse, toxicity related to reactive oxygen species (ROS, inflammatory "amyloid plaque" related processes, catecholamine disequilibrium, etc.

Theoretical research into anticancer activity of diterpenes isolated from the paraiban flora.

Many studies of the scientific literature discuss the anticancer activity of diterpenes inhibiting the Akt/IKK/NF-kappaB pro-survival signaling cascade, mainly by the activation of serine/threonine phosphatase PP2A. The aim of this work was to evaluate and compare the anticancer potential of three atisane, three kaurane and three trachylobane diterpenes extracted from the roots of Xylopia langsdorffiana. Thus, we investigated the reactivity (H-L(GAP) parameter), HOMO atmosphere favorable to neutralize the radical reactivity, and the docking of compounds with PP2A.

Evidence for the involvement of descending pain-inhibitory mechanisms in the attenuation of cancer pain by carvacrol aided through a docking study.

Aims: The present study evaluated the carvacrol (CARV) effect on hyperalgesia and nociception induced by sarcoma 180 (S180) in mice.

Main Methods: Carvacrol treatment (12.5-50mg/kgs.

Prediction of anticancer activity of diterpenes isolated from the paraiban flora through a PLS model and molecular surfaces.

The aim of this work was to predict the anticancer potential of 3 atisane, and 3 trachylobane diterpene compounds extracted from the roots of Xylopia langsdorffiana. The prediction of anticancer activity as expressed against PC-3 tumor cells was made using a PLS model built with 26 diterpenes in the training set. Significant statistical measures were obtained.

Synthesis and preliminary ex vivo evaluation of the spasmolytic activity of 1,3-thiazolium- and 1,3,4-thiadiazolium-5-methylthio- and 5-thioacetate derivatives.

Seven new compounds have been synthetized in satisfactory yields (51-78 %) through the treatment of mesoionic 1,3-thiazolium-5-thiolate (4a-d) and 1,3,4-thiadiazolium- 5-thiolate (10a,b) with chloroacetic acid or methyl iodide: 1,3,4-thiadiazolium-5-methylthio- (11) and 5-thioacetate (12). The structure of the title compounds was elucidated by elemental analysis, IR, (1)H and (13)C NMR spectroscopy. The newly synthesized compounds 5a, 6a, 11 and 12 were evaluated for their ex vivo spasmolytic potential on four isolated smooth muscles (rat aorta and uterus, guinea pig ileum and trachea) and compared with scopolamine.

Antiparasitic activity of natural and semi-synthetic tirucallane triterpenoids from Schinus terebinthifolius (Anacardiaceae): structure/activity relationships.

Leishmaniasis and Chagas are diseases caused by parasitic protozoans that affect the poorest population in the World, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, the discovery of novel, safe and more efficacious drugs is essential. In this work, the in vitro antiparasitic activity and mammalian cytotoxicity of three natural tirucallane triterpenoids, isolated from leaves of Schinus terebinthifolius (Anacardiaceae), and nine semi-synthetic derivatives were investigated against Leishmania (L.

Quantitative structure-sorption relationships of pesticides used in the sugarcane industry in the northern coastal area of Paraíba State, Brazil.

Sorption coefficients (K(oc)) are useful in the prediction of whether a pesticide will remain dissolved in solution or will become adsorbed onto soil particles after its application. Measuring this process experimentally is difficult, expensive and time-consuming. Hence, much effort has been directed toward estimating K(oc) through statistical modelling.

A benzoic acid derivative and flavokawains from Piper species as schistosomiasis vector controls.

The search of alternative compounds to control tropical diseases such as schistosomiasis has pointed to secondary metabolites derived from natural sources. Piper species are candidates in strategies to control the transmission of schistosomiasis due to their production of molluscicidal compounds. A new benzoic acid derivative and three flavokawains from Piper diospyrifolium, P.

Docking and PLS studies on a set of thiophenes RNA polymerase inhibitors against Staphylococcus aureus.

Staphylococcus aureus lives in commensalism with the majority of the population, being recognized as an important pathogen in patients with chronic liver diseases and can cause a deadly infection. The use of antibiotics as rifampin for the chemotherapy of infections caused by S. aureus has resulted in the selection of mutants with resistance.

Schistosomiasis control using piplartine against Biomphalaria glabrata at different developmental stages.

Background: Schistosomiasis is one of the most significant diseases in tropical countries and affects almost 200 million people worldwide. The application of molluscicides to eliminate the parasite's intermediate host, Biomphalaria glabrata, from infected water supplies is one strategy currently being used to control the disease. Previous studies have shown a potent molluscicidal activity of crude extracts from Piper species, with extracts from Piper tuberculatum being among the most active.

Chemometric studies on potential larvicidal compounds against Aedes aegypti.

The mosquito Aedes aegypti (Diptera, Culicidae) is the vector of yellow and dengue fever. In this study, chemometric tools, such as, Principal Component Analysis (PCA), Consensus PCA (CPCA), and Partial Least Squares Regression (PLS), were applied to a set of fifty five active compounds against Ae. aegypti larvae, which includes terpenes, cyclic alcohols, phenolic compounds, and their synthetic derivatives.

SAR, QSAR and docking of anticancer flavonoids and variants: a review.

Flavonoids are phenolic compounds, secondary metabolites of plants that cause several benefits to our health, including helping the treatment against cancer. These pharmacological properties are associated with the ability of flavonoids in attenuating the generation of reactive oxygen species, acting as chelate compounds or affecting the oxi-redox cycle. In spite of the large number of information in term of SAR and QSAR, no recent review has tabulated and discussed in detail these data.

Synthesis, structure-activity relationships (SAR) and in silico studies of coumarin derivatives with antifungal activity.

The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 µg/mL.

Preliminary antifungal and cytotoxic evaluation of synthetic cycloalkyl[b]thiophene derivatives with PLS-DA analysis.

A series of 2-[(arylidene)amino]-cycloalkyl[b]thiophene-3-carbonitriles (2a-x) was synthesized by incorporation of substituted aromatic aldehydes in Gewald adducts (1a-c). The title compounds were screened for their antifungal activity against Candida krusei and Criptococcus neoformans and for their antiproliferative activity against a panel of 3 human cancer cell lines (HT29, NCI H-292 and HEP). For antiproliferative activity, the partial least squares (PLS) methodology was applied.

Self-organizing maps of molecular descriptors for sesquiterpene lactones and their application to the chemotaxonomy of the Asteraceae family.

The Asteraceae, one of the largest families among angiosperms, is chemically characterised by the production of sesquiterpene lactones (SLs). A total of 1,111 SLs, which were extracted from 658 species, 161 genera, 63 subtribes and 15 tribes of Asteraceae, were represented and registered in two dimensions in the SISTEMATX, an in-house software system, and were associated with their botanical sources. The respective 11 block of descriptors: Constitutional, Functional groups, BCUT, Atom-centred, 2D autocorrelations, Topological, Geometrical, RDF, 3D-MoRSE, GETAWAY and WHIM were used as input data to separate the botanical occurrences through self-organising maps.

Caco-2 cells cytotoxicity of nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA).

It is important to determine the toxicity of compounds and co-solvents that are used in cell monolayer permeability studies to increase confidence in the results obtained from these in vitro experiments. This study was designed to evaluate the cytotoxicity of new nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA) in Caco-2 cells to select analogues for further in vitro permeability analyses. In this study, nitrofurantoin and nifuroxazide, in addition to 6 furanic and 6 thiophenic nifuroxazide derivatives were tested at 2, 4, 6, 8 and 10 μg/mL.

Comparative computational studies of 3,4-dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile derivatives as potential antinociceptive agents.

In this study, the antinociceptive properties of 3,4-dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile derivatives 5a-i at doses of 25 and 50 mg/kg were evaluated in mice, using the abdominal constriction test. Molecular modeling studies were also performed using density functional theory calculations. These data provided information about the electrostatic and ionization potentials and were used to compare the antinociceptive activity of the title compounds.