Combinatorial Chemistry & High Throughput Screening - Volume 16, Issue 1, 2013

The catalytic property of Cu(II) Schiff-base complex in an efficient synthesis of 1,8-dioxodecahydroacridines was investigated. The one-pot three component reaction of dimedone, aromatic aldehydes and aromatic amines or ammonium acetate in water afforded the corresponding 1,8-dioxodecahydroacridines with excellent yields. This reaction was carried out in the presence of 1 mol% of catalysts at room temperature. The reusability of the catalysts was demonstrated by a five-run test without loss of its activity. Also, this catalyst possesses several advantages including mild reaction conditions, lower catalytic loading, shorter reaction times, high yield of the products, inexpensive and cleaner (Green chemistry) reactions.

Due to the emergence of multidrug resistance of malaria parasites, there is an urgent need to modify existing antimalarial drugs through structural changes as well as to search new pharmacophores to counteract the induced resistance. In the present work, different quantitative structure-activity relationship (QSAR) models have been developed using a series of 73 1,2,3,4-tetrahydroacridin-9(10H)-one (THA) analogs with well defined antimalarial activity against W2 clone to provide detailed insight into the main structural fragments that impart antimalarial activity to these molecules. To the best of our knowledge, this is first QSAR report of THA analogs as antimalarials. From the developed models, it may be inferred that for an enhancement in the antimalarial activity of the molecules: i) R2 position should be substituted with a bulky group (like phenyl, methoxy, isopropyl, tertiary butyl group) which may be further substituted with electrostatically favored positively charged group; ii) R3 position should be substituted with hydrophobically favored but sterically disfavored group; iii) R4 position should be substituted with positively charged group lacking any carbon atom and iv) R5 position should be substituted with two methyl groups. On the contrary, substitution with bulky group at R6 position may reduce the antimalarial activity. Using the developed models, we have designed and proposed some new compounds which showed good in silico predicted activity. The designed compounds may be experimentally proved to be active and useful THA derivatives as antimalarial compounds.

This work measures and tries to compare the Antioxidant Capacity (AC) of 50 commercial beverages of different kinds: 6 wines, 12 beers, 18 soft drinks and 14 flavoured waters. Because there is no reference procedure established for this purpose, three different optical methods were used to analyse these samples: Total Radical trapping Antioxidant Parameter (TRAP), Trolox Equivalent Antioxidant Capacity (TEAC) and Ferric ion Reducing Antioxidant Parameter (FRAP). These methods differ on the chemical background and nature of redox system. The TRAP method involves the transfer of hydrogen atoms while TEAC and FRAP involves electron transfer reactions. The AC was also assessed against three antioxidants of reference, Ascorbic acid (AA), Gallic acid (GA) and 6-hydroxy-2,5,7,8-tetramethyl- 2-carboxylic acid (Trolox). The results obtained were analyzed statistically. Anova one-way tests were applied to all results and suggested that methods and standards exhibited significant statistical differences. The possible effect of sample features in the AC, such as gas, flavours, food colouring, sweeteners, acidity regulators, preservatives, stabilizers, vitamins, juice percentage, alcohol percentage, antioxidants and the colour was also investigated. The AC levels seemed to change with brand, kind of antioxidants added, and kind of flavour, depending on the sample. In general, higher ACs were obtained for FRAP as method, and beer for kind of sample, and the standard expressing the smaller AC values was GA.

A new, efficient, and solvent-free cyclocondensation reaction of arylmethylidenepyruvic acids with 6- aminouracils is presented that uses a catalytic amount of ZnO nanoparticles (ZnO Nps) as a recyclable catalyst at 70 °C. This protocol has the advantages of high yields (91-98%), easy work-up, very short reaction time (2 h), and using environmentally friendly procedure.

Recent advances in basic and clinical studies have identified Rho kinase (ROCK) as an important target potentially implicated in a variety of cardiovascular diseases and ROCK inhibitors were considered as a pharmacological strategy to prevent and treat cardiovascular diseases. To screen the small molecule compound library against ROCK, a high throughput screening (HTS) campaign was carried out using immobilized metal affinity for phosphochemicals (IMAP)-based time-resolved fluorescence resonance energy transfer (TR-FRET) assay. Z' value and signal to background (S/B) ratio were achieved at 0.76 and 5.27 for the pilot library screening of the most diverse set consisting of 15,040 compounds with a reasonable reconfirmation rate. From this screening campaign, four novel scaffolds, such as 3- nitropyridine, 4-methoxy-1,3,5,-triazine, naphthalene-1,4-dione, and 2,3-dihydro-1H-pyrrolo[2,3-b]quinoxaline, were yielded. Particularly, we found that 3-nitropyridine derivatives possess potent inhibitory activity and selectivity for ROCK. Our findings provide important information for the design of novel ROCK inhibitor.

A thioglycolic acid (TGA)-assisted hydrothermal process has been developed to synthesize cadmium sulfide nanostructures via reaction between a new precursor cadmium (II) phthalate and TGA. X-ray diffraction, transmission electron microscopy, photoluminescence spectroscopy and Fourier transform infrared were employed to characterize the obtained product. The effects of the reactant concentration, mole ratio of TGA to the Cd2+, temperature and reaction time on the morphology, size of particles, and phase of nanocrystalline CdS products were investigated.

The present study deals with the development of an artificial neural network based quantitative structure activity relationship (QSAR) model for virtual screening of active compounds which contain androstenedione carbonskeleton or their similar skeleton at the core. An empirical data modeling (with fitted data mapping) has been performed on the basis of bioassay record for human breast cancer cell line MCF7. The whole experimental data set was considered as test set. Standard feed-forward back-propagation neural network technique was applied to build the model. Leave-One- Out (LOO) cross-validation was performed to evaluate the performance of the model. The mapped model became the basis for selection best mapped compounds followed by development of Pharmacophore specific secondary QSAR model. In the present study, two best mapped molecules ‘4beta-hydroxy Withanolide-E‘ and ‘7, 8-Dehydrocalotropin‘ were used for development of the secondary QSAR model. These secondary-QSAR models were resulted with R2 LOOCV value 0.9845 and 0.9666 respectively. Docking studies, in silico phamacokinetic and toxicity analysis was also done for selected compounds. The screened compounds CID_73621, CID_16757497, CID_301751, CID_390666 and CID_46830222 were found with promising binding affinity value with aromatase with reference to the co-crystallized control compound androstenedione. Due to excellent extent of variance coverage in ANN based QSAR map model, it can be used as a robust non-linear QSAR model for androstenedione carbon-skeleton containing molecules and the protocol can be used to derive secondary QSAR models for other compounds set.

Adsorption of phenolic compounds and chemical analysis of them from a local production cigarette (named by Farvardin cigarette) smoke have been investigated by using perlite filtration. In this research, the mainstream smoke was tested by three filtration methods: Perlite filter, Cambridge filter and general cigarette filter. Then the used filter was extracted by pure methanol as solvent. After that, the extracted solution was analysed by GC-MS. By this consideration, the phenolic derivatives such as phenol, hydroquinone, resorcinol, pyrocatechol, m-cresol, p-cresol and o-cresol were detected. The structure of the perlite filtration after absorption was studied by SEM. In addition, its chemical structure was investigated by XRD and XRF.

In order to find new herbicidally active compounds, a fifteen-member library, focusing on the variation of 3- position substituents of 2,4,5-imidazolidine-trione or 2-thioxo-4,5-imidazolidinedione, was designed and prepared in parallel by the reaction of various ureas or thioureas with oxalyl chloride using solution-phase technology. An interesting and, to the best of our knowledge, unprecedented finding is that a by-product of 1-phenyl-3-propylcarbodiimide was formed during the addition of oxalyl chloride into the solution of 1-phenyl-3-propylthiourea in the presence of triethylamine in dichloromethane. It has been shown that the herbicidal activity of 2,4,5-imidazolidinetriones is about the same as that of their analogous 2-thioxo-4,5-imidazolidinediones. Compound with propyl or isopropyl group at the 3- position of 2,4,5-imidazolidinetrione ring demonstrated good herbicidal activity. The most active compound, 1-(2-fluoro- 4-chloro-5-propargyloxy)-phenyl-3-propyl-2-thioxo-4,5-imidazolidinedione, gave 95% control of the growth of velvetleaf at 200 g/ha in the post-emergence test.