Revue des sciences chimiques

A series of compounds with known experimental IC50 (nM) targeting phosphodiesterase10A (PDE10A) was studied. Recently PDE10A was proposing as a colon cancer drug target. A QSAR model was build using the compounds having as target variable their inhibitory effect on PDE10A expressed as IC50 (nM). A multiple correlation technique was used in order to select the appropriate descriptors for building a regression model. Descriptors used were functional group base descriptors and some centrality descriptors. The regression model was build using artificial neural network regression (ANN). A model with, r2=0.9769, and a standard error deviation of 0.41 was build. Model was used to predict IC50 (nM) for a series of screening resulted compound. Template used for screening was established by generating a hypothesis using the common pharmacophore. The pharmacopohore hypothesis was build using functional groups displacement criteria. Hypothesis resulted was used for virtual screening. Compounds resulted were classified using a score. Best 17 compounds where chosen (when score decreased with 1/3 of best value). A comparison between best PDE10A inhibitor cited in the literature, best dataset compound with inhibitory effect on PDE10A and best compound resulted after screening with best IC50 predicted were analyzed. All three structures were analyzed in complex with PDE10A. Poses were generated using docking. Results demonstrated the importance of Pi-Pi bounds with Phe 696 as being crucial in PDE10A inhibition. The conclusion is sustained by both QSAR model and the common pharmacophore hypothesis.

Three-dimensional quantitative structure–activity relationship (3D-QSAR) and docking methods were performed to study 47 tubulin inhibitors, isatin derivatives with anticancer activity against human monocyte-like histiocytic lymphoma human U937 cells. The established 3D-QSAR model from Comparative Molecular Field Analysis (CoMFA), Comparative Molecular Similarity Index Analysis (CoMSIA) approaches show a significant statistical quality and a satisfying predictive ability, with high correlation coefficient value (R2=0.936, R2=0.970) and cross-validation coefficient value (Q2=0.821, Q2=0.884) of CoMFA and CoMSIA, respectively. The predictive ability of the CoMFA (R2 test=0.607) and CoMSIA (R2 test=0.650) model was confirmed by a test set. The CoMFA, CoMSIA contour maps and docking analyses indicate that the substituent R1 should be oxygen which better than azotes to forms a more potent inhibitor against tubulin enzyme and R2, R3, R4 and R5 substituents should be higher electronegative but R6 should be a bulky aromatic group like a methylnaphthol monosubstituted or disubstitued by OCH3. The interaction information between target and ligand was presented such the useful theoretical references for analyzing to understand the action mechanism, designing new more potent inhibitors and optimizing their activities prior to synthesis.

Synthesis of substituted (4-oxo-3-phenyl-3,4-dihydro quinazolin-2-yl)methyl nitrite derivatives[5(a-j)] have been prepared oxidation reaction of 6-chloro-2-(chloromethyl)-3-[phenyl] quinazolin-4(3H)-one(4) with AgNO3. Compound (5) prepared from starting meterial are 5-chloro-2-[(chloroacetyl)amino]benzoic acid (1) is undergoes to cyclization with acetic anhydride to form 5-chloro-2-[(chloroacetyl)amino]benzoic acid (2) in yield 72%. 5-chloro-2-[(chloroacetyl) amino]benzoic acid(2) undergoes ro cyclisation with acetic anhydride under reflux conidition to form 6-chloro- 2-(chloromethyl)-4H-3,1-benzoxazin-4-one (3) now this compound have been reacted with glycial acetic acid in presence of aniline to form 6-chloro-2-(chloromethyl)-3-[phenyl] quinazolin-4(3H)-one(4). Chareterization done by 1H-NMR, 13C-NMR, IR, MASS spectral analysis. Evaluation of antibacterial activity by Gram-positive bacteria viz. Bacillus subtilis, Bacillus sphaericus and Staphylococcus aureus and three Gram-negative bacteria viz. Pseudomonas aeruginosa, Klebsiella aerogenes and Chromobacterium violaceum and antifungal activity against Candida albicans, Aspergillus fumigates, Trichophyton rubrum and Trichophyton mentagrophytes. Most of the compounds are exihibits more potential activity.

An attempt has been made to synthesise the Schiff base ligand (E)-4-bromo-2-((p-tolylimino)methyl)phenol by the condensation of tolylamine and 5-bromosalicylaldedhye and the coordination behavior its copper complex has been explored by various spectroscopic techniques like UV-Vis., IR, 1H NMR, MS and elemental analysis. The investigative information of the unpredictable demonstrates the arrangement of 1:2 Copper to ligand proportion with the formula [CuL2]. The ligand and the copper chelate have been screened for their antimicrobial activities utilizing disc dissemination technique against gram positive and gram negative bacterial species like Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumonia and parasitic species like Candida and Aspergillus .

This paper presents my comment on the published article, studies on effective decomposition of monazite minerals by variety of phosphate fluxes for simple and direct determination of uranium by LED Fluorimeter. Monazite is a refractory REE-mineral. These REE-bearing minerals contain inclusions of monazite/xenotime. The findings have previously published elsewhere without proper cross referencing /justification in the cited manuscript. It constitutes citation manipulation including plagiarism as well as scientific misconduct. A separate publication and claim by authors dealing with uranium determination in monazite by pulsed fluorimetry (LED fluorimeter) has no novelty/ originality/improvements in the manuscript. Monazite sample decomposition using concentrated sulphuric will be the best option for uranium measurement in such matrices using laser/LED fluorimetry, as it eliminates matrix matching of calibration standards.

2-Aryl-6,7-difluorofenyl-1,3,4-oxadiazolo (3,2-a) (1,3,5)- triazine-5-(6H,7H)- thiones (2a-j) have been orchestrated by the cyclo expansion of para-fluorophenyl 4 –fluoro phenyl isothiocynate and 2-(4-fluorobenzylidine) to (1a-j) 2-amino - 5-phenyl-1,3,4-oxadiazole in dry toluene all the integrated compounds were very much described by their elemental analysis and spectral data. The integrated compounds have been screened for their antifungal action against Phytophthora infestans and Colletotrichum falcatum. Results demonstrated that greatest antifungal activity was appeared by the compounds 2b, 2c, 2g and 2h. These compounds demonstrated 99%, 98%, 99% and 97% hindrance of Phytophthora infestans and 97%, 96%, 98% and 97% Colletotrichum falcatum at 1000 ppm respectively.

All the Actinides (An) are not naturally produced elements, rather most are artificially synthesized by radioactivity (Ra) of some parental and by bombardment of alpha, beta or gamma particles. After bombardment, parental and the decayed radiations are generated or synthesized. However, the parental An are found in natural metal ores. The other An are not just synthesized by Ra of parental An, but also present in radioactive wastes of other metals.

Sixteen azobenzene-p,pꞌ-di[3-substituted-4(3H)quinazolinone-2yl] were synthesized from reaction of azobenzenp, pꞌ-di(3,1-benzoaxzin-4-one-2yl) with amino-moieties nucleophlies, like hydrazinehydrate, hydroxylamine, p,toluidine, p-aminobenzene sulphonamide, 2-pyrimidine, 5-nitro-2-aminopyridine, ethyleneamine,5-(p-bromo) phenyl-2-aminothiazol, p,pꞌ-diamino diphenyl sulphone, quinidine hydrochloride, urea, thiourea, 3,5-dimethyl- 2-phenyl-4-aminopyrazolin-3-one, N(5-methyl-3-isoxazolyl)-p-aminobenzen sulphonamide, semicarbazide and thiosemicarbazide, in a molar ratio (1:2) respectively. azobenzen-p,pꞌ-di(3,1-benzoaxzin-4-one-2yl), was synthesized by following serial synthetic pathway. Reductive-condensation of p-nitrobenzoic acid in basic media give azobenzenp, pꞌ-dicarboxylic acid, then treated with thionyl chloride to give azobenzen-p,pꞌ-diacid chloride. It condensed with anthranilic acid to give azobenzen-p,pꞌ-[(dibenzoic acid-2yl)dicarboxamide], upon treatment with thionyl chloride give azobenzen-p,pꞌ-di(3,1-benzoaxzin-4-one-2yl). All synthesized compounds characterized by FTIR, 1HNMR, 13CNMR and mass spectral analyses. All synthesized azobenzen-p,pꞌ-di(3,1-benzoaxzin-4-one-2yl), and sixteen azobenzenep, pꞌ-di[3-substituted-4(3H)quinazolinone-2yl] compounds, were examined as antibacterial agents against gm(+ve and –ve) bacteria, and antifungal agents. Results showed abroad extended to moderate effects as antibacterial and antifungal agents.

Ethidium Bromide and SYBR Green I are usual examples of ligands that specifically binds to DNA by intercalation. Here we describe that micelles of gangliosides, a lipidic family of sialoglycosphingolipids which are the most important lipids in central nervous system, are able to interact with both, EtBr and SYBR Green I and fluoresce after UV light excitation. The interaction is not affected by the presence of high saline concentration (1M NaCl), a condition which dissociate potential electrostatic interaction between amino and carboxylic acid groups present in EtBr and GM1 respectively; instead, increase the fluorescense of EtBr/GM1 micelles. This result suggests that the EtBr is located inside the hydrophobic core of the micelle. Moreover, the SYBR Green I associated ganglioside micelles does not emit green light as with DNA, but there was a change in the light spectrum towards higher wave lengths, now emitting orange light. It was also found that the interaction with these dyes is not affected when the micelles were preloaded with other molecules (paclitaxel albumin). Moreover, further studies showed that this interaction is not observed with other ionic and nonionic classic detergent micelles, and even the addition of these molecules to GM1 micelles interferes with the described EtBr / GM1 interaction.

Cancer is a dreadful disease causing a major percentage of deaths all over the world. Cancer is the second leading cause of death in the United States, trailing cardiovascular disease. According to National Cancer Institute statistics, over half a million deaths and a million and half new cases are predicted in the year 2017 [1]. The human body is composed of trillions of cells, and they perform specific functions with the aid of proteins. Genes impact the production of these proteins, and an error contained in these genes can yield aberrant versions of these proteins. In some cases, this can result in cancer. A newly diagnosed patient is often concerned for the following reasons: 1) they are afraid of cancer treatments being costly, 2) cancer survival rates are sometimes low and chances of reoccurrence of some cancers are high, and 3) the false paradigm that cancer is incurable.