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In our recent discrimination and classification study on a small set (n=36) of Mallotus apelta, Mallotus paniculatus, Phyllanthus emblica, Phyllanthus reticulatus, Phyllanthus urinaria L. and Phyllanthus amarus fingerprints, the presence of two outliers was observed [1]. Discrimination and classification models were built by means of Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), Classification and Regression Trees (CART) and Soft Independent Modeling of Class Analogy (SIMCA). In order to obtain models that were not influenced by samples of unknown origin, the outliers were not used in the calibration set to build the models. The behavior of the outliers in relation to the model was studied, but the effect of entering or removing the outliers to the calibration set, was not studied in detail. The current study focuses on the effects on the models, when outliers are not removed from the calibration set. For this purpose, on the one hand, the models in [1] were used; on the other models were built using the entire set of fingerprints (outliers included) as calibration set. To study the effects of the outliers on the models, all models were applied on the entire set of fingerprints, resulting in two sets of predicted classes per sample. Besides the predicted class for each sample, class- and overall sensitivities and specificities were computed and used to study the effects of the outliers on the models. Our results indicate that effects on several models are observed, when outliers are kept in the calibration set. Different influences on different models by the outliers are observed. Using SIMCA, classes are modeled separately, affecting only the class borders of the classes containing the outliers, while when using other techniques, effects on samples of other classes can also be observed.

Artemisinin is extracted from the Asian plant Artemisia annua L. It has been proven to be, with its derivatives, the molecules that have shown so far the most powerful activity on malaria, even in its complicated forms and resistance cases. To resolve the problem of low aqueous solubility of this molecule, the use of cyclodextrins (CDs) was envisaged and gave good results in this topic. However, the impact on its stability and in vitro dissolution, important parameters for drug formulation and evaluation, was not evaluated. In this study, stability in accelerated degradation conditions and in vitro dissolution analysis of artemisinin were performed in comparison with complexes of artemisinin and cyclodextrins. The findings of this work allowed us to suggest that CDs improve the stability of artemisinin, especially when it’s in aqueous solution. We also demonstrated the beneficial impact of cyclodextrins on the in vitro dissolution of artemisinin from capsules prepared with rough extracts of A. annua.Keywords: Artemisia annua capsules, malaria, lyoequivalence, dissolution apparatus, storage conditions

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L’huile essentielle de Ocimum canum Sims (Lamiaceae) obtenue par hydrodiffusion à différents moments de la journée a été analysée par GC/FID et GC/SM puis testée sur différentes bactéries par la microtechnique de dilution. Le rendement et la composition chimique de l’huile varient selon le temps et l’ensoleillement. Abondant le matin à 7 heures (1,71±0,01%), le rendement décroît progressivement avec l’augmentation des rayons solaires, jusqu’à son minimum à 13 heures (1,35±0,01%) quand le soleil est au zénith, avant de croître à nouveau à sa valeur la plus élevée (1,78±0,02% à 19 h) au couché du soleil. Plus de 54 composés représentant près de 98% des hydrodiffusats, ont été identifiés dans les différents échantillons. Les principaux sont : α-thujène (5,56 à 7,85%), β-myrcene (2 à 6,94%), δ-3-carène (3,07 à 4,84%), p-cymène (14,61 à 22,8%), g-terpinène (6,05 à 10,7%), carvacrol (7,94 à 30,8%), β-caryophyllène (0,15 à 18,86%) et β- sélinène (2,74 à 14,41%). Les taux de certains constituants comme β-caryophyllène et β-sélinène croissent avec l’ensoleillement contrairement à ceux du carvacrol, p-cymène. Cette variation diurne perturbe la synergie d’action des constituants de l’huile qui présentent une forte activité inhibitrice (0,38 à 7,19 mg/ml) sur Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25923, Acinetobacter baumannii ATCC 19609 et Staphylococcus aureus résistante 1199B NorA. Les huiles obtenues à 7 heures et 19 heures sont les plus efficaces à faible concentration (0,38 à 2,88 mg/ml). Pour la première fois, l'interaction est démontrée entre variation diurne de la composition chimique et propriétés antimicrobiennes de l'huile essentielle de Ocimum canum Sims du Bénin.Keywords: Ocimum americanum, composés volatils, Chémotype à carvacrol Variation diurne-Activité antibactérienne

There are many protein ligands and/or drugs described with very different affinity to a large number of target proteins or receptors. In this work, we selected Ligands or Drug-target pairs (DTPs/nDTPs) of drugs with high affinity/non-affinity for different targets. Quantitative Structure-Activity Relationships (QSAR) models become a very useful tool in this context to substantially reduce time and resources consuming experiments. Unfortunately most QSAR models predict activity against only one protein target and/or have not been implemented in the form of public web server freely accessible online to the scientific community. To solve this problem, we developed here a multi-target QSAR (mt-QSAR) classifier using the MARCH-INSIDE technique to calculate structural parameters of drug and target plus one Artificial Neuronal Network (ANN) to seek the model. The best ANN model found is a Multi-Layer Perceptron (MLP) with profile MLP 20:20-15-1:1. This MLP classifies correctly 611 out of 678 DTPs (sensitivity=90.12%) and 3083 out of 3408 nDTPs (specificity=90.46%), corresponding to training accuracy=90.41%. The validation of the model was carried out by means of external predicting series. The model classifies correctly 310 out of 338 DTPs (sensitivity=91.72%) and 1527 out of 1674 nDTP (specificity = 91.22%) in validation series, corresponding to total accuracy = 91.30% for validation series (predictability). This model favorably compares with other ANN models developed in this work and Machine Learning classifiers published before to address the same problem in different aspects. We implemented the present model at web portal Bio-AIMS in the form of an online server called: Non-Linear MARCH-INSIDE Nested Drug-Bank Exploration & Screening Tool (NL MIND-BEST), which is located at URL: http://miaja.tic.udc.es/Bio-AIMS/NL-MIND-BEST.php. This online tool is based on PHP/HTML/Python and MARCH-INSIDE routines. Finally we illustrated two practical uses of this server with two different experiments. In experiment 1, we report by first time Quantum QSAR study, synthesis, characterization, and experimental assay of antiplasmodial and cytotoxic activities of oxoisoaporphine alkaloids derivatives as well as NL MIND-BEST prediction of potential target proteins. In experiment 2, we report sampling, parasite culture, sample preparation, 2-DE, MALDI-TOF, and -TOF/TOF MS, MASCOT search, MM/MD 3D structure modeling, and NL MIND-BEST prediction for different peptides a new protein of the found in the proteome of the human parasite Giardia lamblia, which is promising for anti-parasite drug-targets discovery.

The antibacterial and the free radical scavenging activities of the alcoholic extract, total alkaloid extract and three compounds isolated from Mitracarpus scaber were evaluated using the p-iodonitrotetrazolium method and the DPPH method. The extracts and the three compounds identified as methoxy-4-acetophenon, 3,4,5-trimethoxybenzoic acid, azaanthraquinone were tested in vitro against five micro organisms. Azaanthraquinone showed the most interesting activity with minimum inhibitory concentrations values of 7.5 μg/ml, 19 μg/ml, 38 μg/ml and 150 μg/ml on Dermatophilus congolensis, Staphylococcus aureus, Enteroccocus feacalis, Escherichia coli and Pseudomonas aeruginosa, respectively. On the other hand, the three tested compounds showed mild scavenging activity in the DPPH test, with IC50 values between 12 μg/ml and 45.74 μg/ml.Keywords: Mitracarpus scaber, azaanthraquinone, antimicrobial activity, antioxidant activity.

A new lignan dimer, bilariciresinol (1), was isolated from the leaves of Mallotus philippensis, along with platanoside (2), isovitexin (3), dihydromyricetin (4), bergenin (5), 4-O-galloylbergenin (6), and pachysandiol A (7). Their structures were elucidated by spectroscopic experiments including 1D and 2D NMR and FTICR-MS.

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BACKGROUND: Trachylobane diterpenes are secondary metabolites, quite rare in nature, and their bioactivities are poorly understood. Recently, we have described the cytotoxic activity of ent-trachyloban-3beta-ol isolated from the leaves of Croton zambesicus, a plant used in African folk medicine. MATERIALS AND METHODS: Cell viability on several cell lines, cell morphology, DNA laddering, annexin Vand caspase-3 activation experiments were undertaken in order to analyse the cytotoxicty of trachylobane diterpene and to determine if this compound is able to induce apoptosis. RESULTS: ent-Trachyloban-3beta-ol exerts a dose-dependent cytotoxic effect, which varies between cell lines. Induction of apoptosis in HL-60 cells could be detected at a concentration of 50 microM after 24-h treatment. CONCLUSION: We show here, for the first time, that a trachylobane diterpene is able to induce apoptosis in human promyelocytic leukemia cells via caspase-3 activation in a concentration-dependent manner.