With the aim to find out the structural features for the MAO inhibitory activity and selectivity, in the present communication we report the design, synthesis and pharmacological evaluation of a new series of coumarin derivatives with 4-methyl or cycloalkene or benzene ring condensed in the 3,4 position. The substituents in this new scaffold were introduced in the 5, 7 and/or 8 positions of the coumarin moiety. The synthesized compounds 1-13 were evaluated as MAO A and B inhibitors using clorgyline and selegiline, respectively, as reference inhibitors, showing, most of them, activities in the nanomolar range. Compounds 6 (IC50 = 1.18 nM) and 10 (IC50 = 1.48 nM), show higher activity than selegiline (IC50 = 19.60 nM), and high MAO-B selectivity with 100-fold and 1600-fold inhibition levels, with respect to the MAO-A isoform.

The condensation of substituted pyrazinecarboxylic acid chlorides with ring substituted anilines yielded nine substituted pyrazinecarboxylic acid amides. The photo-synthesis inhibition activity of a series of pyrazine derivatives was investigated. The synthesis, analytical and biological data of the newly synthesized compounds are presented in this paper. The most active inhibitor of the oxygen evolution rate in spinach chloroplasts was 2-(5-methyl-pyrazine-2-carboxamido)benzoic acid (9, IC50 = 85.0 µmol·L-1).

Skin penetration enhancers are used to allow formulation of transdermal delivery systems for drugs that are otherwise insufficiently skin-permeable. The series of seven esters of substituted 6-aminohexanoic acid as potential transdermal penetration enhancers was formed by multistep synthesis. The general synthetic approach of all newly synthesized compounds is presented. Structure confirmation of all generated compounds was accomplished by 1H NMR, 13C NMR and IR spectroscopy.

Some (5-arylalkylidene-4-oxo-2-thioxothiazolidin-3-yl)acetic acids were prepared as potential antimicrobial compounds. General synthetic approach of all synthesized compounds is presented. All the discussed rhodanine-3-acetic acid derivatives were analyzed using the reversed phase high performance liquid chromatography (RP-HPLC) method for the lipophilicity measurement. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using end-capped non-polar C18 stationary RP column. RP-HPLC retention parameter log k (the logarithm of capacity factor k) is compared with log P values calculated in silico. The relationships between the lipophilicity and chemical structure of the studied compounds are discussed as well.

The aim of this work is to study the potential of several natural matrixes as sources of antioxidants to use as plastic additives. The matrixes studied were: green tea, black tea, Lippia citriodora and Hyericum androsaemum. The phenolic profiles were studied by High Performance Liquid Chromatography (HPLC) using ultraviolet (UV) diode array and Fluorescence (FL) detectors.

The synthesis of three new trisazo dyes containing 4,4'-diaminobenzanilide as middle component is presented. The dyes were analyzed by thin layer chromatography (TLC), electronic spectra (VIS) and their structure was confirmed by mass spectroscopy (FABS). The toxicity of the synthesized dyes was evaluated by biological tests, using the process of metamorphosis in the marine Hydrozoon Hydractinia echinata. The concentration (termed by MRC50) at which the synthesized dyes (and their precursors) antagonize metamorphosis induction was determined. The obtained results indicate that these dyes exhibit toxicity values which are lying in a low average lows scale of toxicity.

The study of type III RNases constitutes an important area in molecular biology. It is known that the pac1+ gene encodes a particular RNase III that shares low amino acid similarity with other genes despite having a double-stranded ribonuclease activity. Bioinformatics methods based on sequence alignment may fail when there is a low amino acidic identity percentage between query sequence and others with similar functions (remote homologues) or a similar sequence is not recorded in the database. Quantitative Structure-Activity Relationships (QSAR) applied to protein sequences may allow an alignment-independent prediction of protein function. These sequences QSAR like methods often use 1D sequence numerical parameters as the input to seek sequence-function relationships. However, previous 2D representation of sequences may uncover useful higher-order information. In the work described here we calculated for the first time the Spectral Moments of a Markov Matrix (MMM) associated with a 2D-HP-map of a protein sequence. We used MMMs values to characterize numerically 81 sequences of type III RNases and 133 proteins of a control group. We subsequently developed one MMM-QSAR and one classic Hidden Markov Model (HMM) based on the same data. The MMM-QSAR showed a discrimination power of RNAses from other proteins of 97.35% without using alignment, which is a result as good as for the known HMM techniques. We also report for the first time the isolation of a new Pac1 protein (DQ647826) from Schizosaccharomyces pombe, strain 428-4-1. The MMM-QSAR model predicts the new RNase III with the same accuracy as other classical alignment methods. Experimental assay of this protein confirms the predicted activity. The present results suggest that MMM-QSAR models may be used for protein function annotation avoiding sequence alignment with the same accuracy of classic HMM models.

Protozoan parasites have been one of the most significant public health problems for centuries and several of human infections causes by them are globally massive in their impact. The most of the current drugs used to treat these illness are decades old and have many limitations, including the emergence of drug resistance, severe sideeffects, low-to-medium efficacy, parenteral mode of administration, price, etc. These drugs have been largely neglected for drug development because they affect poor people in poor regions of the world where there is a small market for this kind of drugs. Therefore, nowdays there is a pressing need for identifying and developing new drugbased antiprotozoan therapies. In an effort to overcome this problem, the main purpose of this study is to develop a QSARs-based ensemble classifier for antiprotozoan druglike compounds from a heterogeneous series of compounds. Here, we use some of the TOMOCOMD-CARDD molecular descriptors and linear discriminat analisis (LDA) to derive individual linear classification functions in order to discriminate between antiprotozoan and nonantiprotozoan compounds, and so as to enable computational screening from virtual combinatorial datasets and/or existing drugs already approved. All studies were carried out taken into account the OECD principle in order for characterizing every obtained QSARs. In first time, a wide-spectrum benchmark database of 680 organic chemicals having great structural variability, 254 of them antiprotozoan agents and 426 compounds having other clinical uses, was analyzed and presented as a helpful tool, not only for theoretical chemists but also for other researchers in this area. This series of compounds was processed by a k-means cluster analysis in order to design training and predicting sets. In total, seven discriminant functions were obtained, by using the whole set of atom-based linear indices. All the LDA-based QSAR models show accuracies above 85% in the training set and values of Matthews correlation coefficients (C) varying from 0.70-0.86. The external validation set shows globally rather-good classifications around 80% (92.05% for best equation). Later, we developed a multi-agent QSAR classification system, in which the individual QSAR outputs are the inputs of the aforementioned fusion approach. Finally, the fusion model was used for the identification of a novel generation of lead-like antiprotozoans by using ligand-based virtual screening of small-molecules ‘available’ (with synthetic feasibility) in our ‘in-house’ library. A new molecular subsystem (quinoxalinones) was then theoretically selected like promising lead series, which were subsequently synthesized, structurally characterized, and experimentally assayed using an in vitro screening that take into consideration a battery of four parasite-based assays. The chemicals 11(12) and 16 are the most active (hits) against apicomplexa (sporozoa) and mastigophora (flagellata) subphylum parasites, respectively. Both compounds had shown rather good activities in the every protozoan in vitro panel and they didn't depict unspecific cytotoxicity to macrophages. This result opens a door to a virtual study considering a higher variability of the structural core already evaluated, as well as of other chemicals not included in this study. We conclude that the approach described here seems to be a promising esamble QSAR-clasifier for the molecular discovery of novel classes of broad –antiprotozoan– spectrum drugs, which may meet the dual challenges posed by drug-resistant parasites and the rapid progression of protozoan illnesses.

A series of 2’-hydroxychalcones was synthesized and screened for their in vitro inhibitory effects on PGE2 production from RAW 264.7 cells induced by LPS. Structure–activity relationship study suggested that inhibitory activity of PGE2 formation was governed to a greater extent by the substituent on B ring of the chalcone template, and most of the active compounds have at least two methoxyl or benzyloxyl groups on B ring. The relationship between chalcone structures and their PGE2 inhibitory activity was also interpreted by docking study on cyclooxygenase 2.

The series of twelve ring-substituted 4-hydroxy-1H-quinolin-2-one derivatives were prepared. The synthetic procedures of the compounds are presented. All the prepared quinoline derivatives were analyzed using RP-HPLC method for the lipophilicity measurement and their lipophilicity was determined. The prepared compounds were tested for their photosynthesis-inhibiting activity (the inhibition of photosynthetic electron transport in spinach chloroplasts (Spinacia oleracea L.). The relationships between the lipophilicity and the chemical structure of the studied compounds are discussed as well as the structure-activity relationships (SAR) between the chemical structure and the biological activities of the evaluated compounds.