Topomer CoMFA and Virtual Screening Studies of Azaindole Class Renin Inhibitors.
This study also adopted the methodology of fragment-based drug design (FBDD) to virtual screen new renin inhibitors by using Topomer Search technology. The R1-group of the compound No. 13 with the highest activity was chosen as the basic scaffold, and its remaining R2-group acted as a query to screen 142,025 molecules of ZINC database for similar fragments. The obtained 30 fragments with the highest R2-group contribution values were added to the basic scaffold respectively. Finally 30 new azaindole compounds with potent high activities were obtained. Further the binding modes were studied by using Surflex-Dock. The docking...
Source: Combinatorial Chemistry and High Throughput Screening - January 6, 2014 Category: Chemistry Authors: Xiang Y, Song J, Zhang Z Tags: Comb Chem High Throughput Screen Source Type: research

Editorial: scientific misconduct.
PMID: 24410067 [PubMed - in process] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - January 1, 2014 Category: Chemistry Authors: Chaguturu R Tags: Comb Chem High Throughput Screen Source Type: research

Classification SAR Modeling of Diverse Quinolone Compounds for Antimalarial potency Against Plasmodium Falciparum.
Abstract Both a development of resistance to artemisinin monotherapy and lack of effective vaccine against malaria have created the urgent need for the development of new and efficient antimalarial agents. In this background, we have developed here a linear discriminant analysis (LDA) model and a few 3D-pharmacophore models for the classification of diverse quinolone compounds based on their antimalarial potency against Plasmodium falciparum. The discriminant model shows 70% correct classification for the test set compounds into higher active and lower active analogues. The best pharmacophore model (Hypo-1) with a...
Source: Combinatorial Chemistry and High Throughput Screening - December 29, 2013 Category: Chemistry Authors: Aher RB, Roy K Tags: Comb Chem High Throughput Screen Source Type: research

H3PW12O40-Catalyzed Multicomponent Reaction for Efficient Synthesis of Highly Substituted Piperidines.
Abstract A simple, diastereoselective, inexpensive, and efficient route for the synthesis of highly functionalized piperidines by the condensation of β-keto-esters, aromatic aldehydes and anilines using H3PW12O40 as a catalyst is described. The catalyst could be easily recovered after completion of the reaction and reused without a considerable change in its activity. Furthermore, in most cases the piperidine precipitates out of solution. PMID: 24372051 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - December 29, 2013 Category: Chemistry Authors: Khaksar S, Baghbanian SM, Barsan N Tags: Comb Chem High Throughput Screen Source Type: research

GC-MS Lipidomic Profiling of the Echinoderm Marthasterias glacialis and Screening for Activity against Human Cancer and Non-cancer Cell Lines.
de PB Abstract Marine organisms have been increasingly regarded as an excellent source of bioactive molecules for human health. As part of an on-going study to elucidate the chemical composition and biological activity of this organism, we report here the lipidomic profile of this organism and screening for anticancer activity. Two classes of biologically active metabolites were identified and quantified by a GC-MS optimized method for screening several classes of metabolites in a single run. Free fatty acids and sterols were found, including ergosterol, β-sitosterol and cholesterol derivatives, some of which...
Source: Combinatorial Chemistry and High Throughput Screening - December 28, 2013 Category: Chemistry Authors: Pereira DM, Correia-da-Silva G, Valentão P, Teixeira N, Andrade PB Tags: Comb Chem High Throughput Screen Source Type: research

Novel Approach for the Synthesis of Pyrrolo[2,1-c][1,4]Benzoxazines and Pyrrolo[1,2-a]Quinoxalines.
Abstract An efficient synthesis of alkyl 4,5-dihydro-4-oxo-2-phenylpyrrolo[2,1-c][1,4]benzoxazine-3-carboxylates and alkyl 4,5-dihydro-4-oxo-2-phenylpyrrolo[1,2-a]quinoxaline-3-carboxylates is described. This involves a three-component reaction between o-aminophenols or o-phenylenediamine, acetylenic esters and β-nitrostyrene derivatives using p-toluene sulfonic acid as a catalyst. PMID: 24369957 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - December 27, 2013 Category: Chemistry Authors: Sanaeishoar T, Adibi-Sedeh S, Karimian S Tags: Comb Chem High Throughput Screen Source Type: research

One-Pot Multi-Component Route to Propargylamines Using Zinc Oxide Under Solvent-Free Conditions.
Abstract In this paper, commercially available ZnO was found to be a highly effective catalyst for three-component coupling reactions of alkynes, aldehydes/or ketone and amines (A3-coupling) via C-H activation. The reactions could be applied to both aromatic and aliphatic aldehydes. Nearly quantitative yields of the desired products were obtained in most cases. No co-catalyst or activator is required, and water is the only by-product in the reactions. Heterogeneous nature of the catalyst made it reusable for further chemical reactions. PMID: 24344992 [PubMed - as supplied by publisher] (Source: Combinatorial ...
Source: Combinatorial Chemistry and High Throughput Screening - December 16, 2013 Category: Chemistry Authors: Hosseini-Sarvari M, Moeini F Tags: Comb Chem High Throughput Screen Source Type: research

Computational Evidence for the Reactivation Process of Human Acetylcholinesterase Inhibited by Carbamates.
Abstract Acetylcholinesterase (AChE) is responsible for hydrolysis of acetylcholine (ACh), a function, which if disrupted, leads to cholinergic syndrome. Carbamates (CB) and organophosphorus compounds (OP) are AChE inhibitors, toxic and capable of causing severe poisoning or death to exposed individuals. The AChE reactivation is considered the main function of the oximes. In case of poisoning by CB, there is no consistent data in the literature for an oxime reactivation mechanism. In this work, we evaluated the affinity and reactivity of oximes with activity already reported against AChE inhibited by the OP chemic...
Source: Combinatorial Chemistry and High Throughput Screening - December 16, 2013 Category: Chemistry Authors: Matos KS, da Cunha EF, Abagyan R, Ramalho TC Tags: Comb Chem High Throughput Screen Source Type: research

Liquid-phase Combinatorial Library Synthesis: Recent Advances and Future Perspectives.
Abstract Liquid-phase combinatorial library synthesis is developed into the viable alternatives or adjunct across the broad spectrum of polymer-supported organic chemistry. It involves the use of soluble polymer supports in the combinatorial synthesis of peptides and small-molecular library compounds which acts as catalyst and reagent supports. It also involves high-throughput biological screening which generates and evaluates chemical leads for drug discovery development. In this review, liquid-phase combinatorial synthesis is shown as most efficient method of choice for the synthesis of most of the combinatorial...
Source: Combinatorial Chemistry and High Throughput Screening - November 17, 2013 Category: Chemistry Authors: Barot KP, Nikolova S, Ivanov I, Ghate MD Tags: Comb Chem High Throughput Screen Source Type: research

Advances in Nanomaterial-Based Microwaves and Infrared Wave-Assisted Tryptic Digestion for Utrafast Proteolysis and Rapid Detection by MALDI-MS.
Abstract The unique physico-chemical properties of nanomaterials have significantly impacted in electromagnetic waves (microwave and infrared waves)-assisted tryptic digestion approaches by using them as heat absorbers to expedite digestion and as affinity probes to enrich digested proteins prior to MALDI-MS analysis. We review recent developments in electromagnetic waves (microwaves and infrared waves)-assisted proteolysis using nanomaterials as heat absorbers and as affinity probes for analysis of digested proteins in MALDI-MS. New trends in ultrafast proteolysis (nonphosphoproteins- lysozyme, cytochrome c, myog...
Source: Combinatorial Chemistry and High Throughput Screening - November 10, 2013 Category: Chemistry Authors: Kailasa SK, Hui-Fen W Tags: Comb Chem High Throughput Screen Source Type: research

A Genetic Algorithm- Back Propagation Artificial Neural Network Model to Quantify the Affinity of Flavonoids toward P-glycoprotein.
Abstract Flavonoids, the most diverse class of plant secondary metabolites, exhibit high affinity toward the purified cytosolic NBD2(C-terminal nucleotide-binding domain) of P-glycoprotein (P-gp). To explore the affinity of flavonoids for P-gp, quantitative structure-activity relationships (QSARs) models were developed using back-propagation artificial neural networks (BPANN) and multiple linear regression (MLR). Molecular descriptors were calculated using PaDEL-Descriptor, and the number of descriptors was then reduced using a genetic algorithm (GA) and stepwise regression. The MLR (R2=0.855, q2=0.8138, Rext2=0.6...
Source: Combinatorial Chemistry and High Throughput Screening - November 8, 2013 Category: Chemistry Authors: Shen J, Cui Y, Gu J, Li Y, Li L Tags: Comb Chem High Throughput Screen Source Type: research

Letter from the Section Editor of Combinatorial / Medicinal Chemistry: December 2013.
PMID: 24200151 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - November 6, 2013 Category: Chemistry Authors: Afantitis A Tags: Comb Chem High Throughput Screen Source Type: research

Three-Component Synthesis of Spiro[Indoline-3,4'-Pyrano[3,2-b]Pyran]-2,8'-Diones Using a One-Pot Reaction.
Abstract A one-pot, three-component reaction of an isatine and kojic acid with an active methylene compound such as ethyl cyanoacetate, methyl cyanoacetate and malononitrile in methanol using catalytic amount of DABCO to give 2'-amino-6'-(hydroxymethyl)-8'H-spiro[indoline-3,4'-pyrano[3,2-b]pyran]-2,8'-diones in good to excellent yields under reflux conditions, is described. PMID: 24164049 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - October 27, 2013 Category: Chemistry Authors: Rahmati A, Khalesi Z, Kenarkoohi T Tags: Comb Chem High Throughput Screen Source Type: research

An In Silico Appraisal of Azoic and Disulphide Derivatives for Anticancer Activity Against HPV E6 Oncoprotein to Medicate Cervical Cancer.
Abstract Cervical cancer is the second largest form of cancer to infest the leading cause of death in women worldwide. There are many causes of cancer but viruses are the most common among them. Human papillomaviruses (HPVs) are found to be the causative organism in almost 99.7% of the cases. HPV16 is the most frequent HPV type in malignant neoplastic growth in about 60% of cervical carcinomas cases. There is limited success achieved in surgical removal or by immune modulation and more effective therapies are under investigation. Observing the mortality rate we theorize a need for alternative treatment approaches ...
Source: Combinatorial Chemistry and High Throughput Screening - October 27, 2013 Category: Chemistry Authors: Choudhury AD, Choudhury MD, Chetia P, Chowdhury A, Talukdar AD Tags: Comb Chem High Throughput Screen Source Type: research

Combinatorial Synthesis of Benzimidazole-azo-phenol Derivatives as Antifungal Agents.
Abstract A chemically diverse library of benzimidazole-azo-phenol derivatives was efficiently prepared and screened for their antifungal activities against five phytopathogenic fungi. Some compounds exhibited the potent antifungal activities. As compared with a commercially available agricultural fungicide, hymexazol, especially compound V-5 showed the most promising broad-spectrum antifungal activities against five phytopathogenic fungi. The EC50 values of V-5 against F. graminearum, A. solani, V. mali, B. cinerea, and C. lunata were 0.09, 0.08, 0.06, 0.07, and 0.11 μmol/mL, respectively. PMID: 24152176 [...
Source: Combinatorial Chemistry and High Throughput Screening - October 20, 2013 Category: Chemistry Authors: Ke Y, Zhi X, Yu X, Ding G, Yang C, Xu H Tags: Comb Chem High Throughput Screen Source Type: research

Synthesis of 2-Amino-4H-Chromen-4-yl Phosphonats via C-P Bond Formation Catalyzed by Nano-Rods ZnO Under Solvent-Free Condition.
Abstract One-pot, three-component reactions of structurally diverse salicylaldehydes with malononitrile (or ethylcyanoacetate) and diethyl (or dimethyl) phosphate are carried out in the presence of nano-rods ZnO as an efficient catalyst for the synthesis of biologically interesting 2-amino-4H-chromen-4-yl phosphonate derivatives. The value of this method lies in its mild and environmentally benign reaction, simple procedure, good yields, and ease of handling. PMID: 24152177 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - October 20, 2013 Category: Chemistry Authors: Hosseini-Sarvari M, Roosta A Tags: Comb Chem High Throughput Screen Source Type: research

Classification of Aurora B Kinase Inhibitors Using Computational Models.
Abstract Using Self-Organizing Map (SOM) and Support Vector Machine (SVM), four classification models were built to predict whether a compound is an active or weakly active inhibitor of Aurora B kinase. A dataset of 679 Aurora B kinase inhibitors was collected, and randomly split into a training set (278 active and 204 weakly active inhibitors) and a test set (109 active and 88 weakly active inhibitors). Based on 19 selected ADRIANA.Code descriptors and 135 MACCS fingerprints, all the four models showed a good prediction accuracy of over 87% on the test set. It benefited from the advantages of two different types ...
Source: Combinatorial Chemistry and High Throughput Screening - October 20, 2013 Category: Chemistry Authors: Liu R, Nie X, Zhong M, Hou X, Xuan S, Yan A Tags: Comb Chem High Throughput Screen Source Type: research

Combination Therapy: The propitious rationale for drug development.
Abstract Therapeutic options for many infections are extremely limited and at crisis point. We run the risk of entering a second pre-antibiotic era. There had been no miracle drug for the patients infected by resistant microbial pathogens. Most of the very few new drugs under development have problems with their toxicity, or pharmacokinetics and pharmacodynamics. We are already decades behind in the discovery, characterization and development of new antimicrobials. In that scenario, we could not imagine surviving without newer and effective antimicrobial agents. Bacteria have been the champions of evolution and ar...
Source: Combinatorial Chemistry and High Throughput Screening - October 11, 2013 Category: Chemistry Authors: Phougat N, Khatri S, Singh A, Dangi M, Kumar M, Dabur R, Chhillar AK Tags: Comb Chem High Throughput Screen Source Type: research

Digital Holographic Microscopy: a quantitative label-free microscopy technique for phenotypic screening.
Abstract Digital Holographic Microscopy (DHM) is a label-free imaging technique allowing visualization of transparent cells with classical imaging cell culture plates. The quantitative DHM phase contrast image provided is related both to the intracellular refractive index and to cell thickness. DHM is able to distinguish cellular morphological changes on two representative cell lines (HeLa and H9c2) when treated with doxorubicin and chloroquine, two cytotoxic compounds yielding distinct phenotypes. We analyzed parameters linked to cell morphology and to the intracellular content in endpoint measurements and furthe...
Source: Combinatorial Chemistry and High Throughput Screening - October 3, 2013 Category: Chemistry Authors: Rappaz B, Breton B, Shaffer E, Turcatti G Tags: Comb Chem High Throughput Screen Source Type: research

Mechanistic insights into mode of action of a potent natural antagonist of orexin receptor-1 by means of high throughput screening and molecular dynamics simulations.
Abstract Insomnia is one of the most common clinical problems being faced by people all over the world. It adversely affects the routine life of these patients giving rise to even other health issues like hypertension, diabetes, obesity, depression, heart attack, and stroke. Orexin receptor-1 (OX1R), a noteworthy drug target, when inhibited can promote sleepiness in people suffering from such conditions. OX1R is a G-protein coupled receptor which is conserved throughout the mammalian species and is located primarily in hypothalamus and locus coeruleus. The present study aims at identifying potent natural-origin in...
Source: Combinatorial Chemistry and High Throughput Screening - October 3, 2013 Category: Chemistry Authors: Dhanjal JK, Grover S, Paruthi P, Sharma S, Grover A Tags: Comb Chem High Throughput Screen Source Type: research

Receptor Guided 3D-QSAR Analysis of Thieno[2,3-b]pyridine-5-carbonitrile Inhibitors of Protein Kinase C theta (PKC-θ).
Receptor Guided 3D-QSAR Analysis of Thieno[2,3-b]pyridine-5-carbonitrile Inhibitors of Protein Kinase C theta (PKC-θ). Comb Chem High Throughput Screen. 2013 Aug 29; Authors: Silakari O, Chand S, Kaur M, Vyas B, Silakari P, Bahia MS Abstract In the present study, receptor induced 3D-QSAR model was developed for a set of 46 thieno[2,3-b]pyridine-5-carbonitrile PKC-θ inhibitors, to explore the structural requirements of the molecules necessary for PKC-θ inhibition. Since the chemical nature of the studied molecules was different from the crystal ligand of the selected protein, induced fit d...
Source: Combinatorial Chemistry and High Throughput Screening - August 29, 2013 Category: Chemistry Authors: Silakari O, Chand S, Kaur M, Vyas B, Silakari P, Bahia MS Tags: Comb Chem High Throughput Screen Source Type: research

Modulators of the MicroRNA Biogenesis Pathway Via Arrayed Lentiviral Enabled RNAi Screening for Drug and Biomarker Discovery.
Abstract MicroRNAs (miRNAs) are small endogenous and conserved non-coding RNA molecules that regulate gene expression. Although the first miRNA was discovered well over sixteen years ago, little is known about their biogenesis and it is only recently that we have begun to understand their scope and diversity. For this purpose, we performed an RNAi screen aimed at identifying genes involved in their biogenesis pathway with a potential use as biomarkers. Using a previously developed miRNA 21 (miR-21) EGFP-based biosensor cell based assay monitoring green fluorescence enhancements, we performed an arrayed short hairp...
Source: Combinatorial Chemistry and High Throughput Screening - August 26, 2013 Category: Chemistry Authors: Shum D, Bhinder B, Djaballah H Tags: Comb Chem High Throughput Screen Source Type: research

Sonochemical Method for Preparation of Copper Indium Sulfide Nanoparticles and their Application for Solar Cell.
Abstract In this paper, CuInS2 (CIS) nanoparticles was synthesized successfully via a new copper precursor [bis(acetylacetonato)copper(II)], [Cu(acac)2]; at room temperature by ultrasonic method. The effect of sulfur source, solvent, and reaction time was investigated on product morphology and particle size. A series of analysis were performed to characterize the CuInS2 microsphere including X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and photoluminescence (PL) spectroscopy. CuInS2 nanoparticles were prepared and coated on FTO. Later, the coated FTO was sinte...
Source: Combinatorial Chemistry and High Throughput Screening - August 20, 2013 Category: Chemistry Authors: Amiri O, Salavati-Niasari M, Sabet M, Ghanbari D Tags: Comb Chem High Throughput Screen Source Type: research

A High Content Assay to Assess Cellular Fitness.
Abstract A universal process in experimental biology is the use of engineered cells; more often, stably or transiently transfected cells are generated for the purpose. Therefore, it is important that cell health assessment is conducted to check for stress mediated by induction of heat shock proteins (Hsps). For this purpose, we have developed an integrated platform that would enable a direct assessment of transfection efficiency (TE) combined with cellular toxicity and stress response. We make use of automated microscopy and high content analysis to extract from the same well a multiplexed readout to assess and de...
Source: Combinatorial Chemistry and High Throughput Screening - August 16, 2013 Category: Chemistry Authors: Antczak C, Mahida JP, Singh C, Calder PA, Djaballah H Tags: Comb Chem High Throughput Screen Source Type: research

Probing an Artificial Polypeptide Receptor Library Using a Series of Novel Histamine H3 Receptor Ligands.
Abstract An artificial polypeptide receptor (APR) library was created by using the self-organization of N-lipidated peptides attached to cellulose via m-aminophenylamino-1,3,5-triazine. The response of the library was probed using a series of novel H3 receptor ligands. Since no guidelines on how to design an APRs selective vs. certain receptor types exist, a diverse set of amino acids (Ala, Trp, Pro, Glu, His, Lys and Ser) were used and coupled with one of three gating fatty acids (palimitic, ricinoleic or capric). A competitive adsorption-desorption of an appropriate reporter dye was used for the indirect visuali...
Source: Combinatorial Chemistry and High Throughput Screening - July 17, 2013 Category: Chemistry Authors: Bak A, Daszykowski M, Kaminski Z, Kononowicz KK, Kuder K, Fraczyk J, Kolesinska B, Ciosek P, Polanski J Tags: Comb Chem High Throughput Screen Source Type: research

Systematic Analysis of RNAi Reports Identifies Dismal Commonality at Gene-Level & Reveals an Unprecedented Enrichment in Pooled ShRNA Screens.
Systematic Analysis of RNAi Reports Identifies Dismal Commonality at Gene-Level & Reveals an Unprecedented Enrichment in Pooled ShRNA Screens. Comb Chem High Throughput Screen. 2013 Jul 8; Authors: Bhinder B, Djaballah H Abstract RNA interference (RNAi) has opened promising avenues to better understand gene function. Though many RNAi screens report on the identification of genes, very few, if any, have been further studied and validated. Data discrepancy is emerging as one of RNAi main pitfalls. We reasoned that a systematic analysis of lethality-based screens, since they score for cell death, would ex...
Source: Combinatorial Chemistry and High Throughput Screening - July 8, 2013 Category: Chemistry Authors: Bhinder B, Djaballah H Tags: Comb Chem High Throughput Screen Source Type: research

In Silico Identification of Potential Dynamin-Related Protein 1 Antagonists: Implications for Diseases Involving Mitochondrial Dysfunction.
In this study, an integrated in silico strategy that includes homology modeling, pharmacophoric, docking analysis and molecular dynamics simulations was employed in designing the potential Drp1 inhibitors. A homology model of Drp1 was generated employing crystal structure of dynamin protein as a template. Pharmacophoric features were developed for the GTPase domain of dynamin-related protein 1 and were used to screen ZINC-database. The obtained hits were docked to the same domain. The binding mode analysis of these ligands showed all the essential binding interactions required in the inhibition of Drp1. Furthermore, explic...
Source: Combinatorial Chemistry and High Throughput Screening - July 8, 2013 Category: Chemistry Authors: Pradeep H, Rajanikant GK Tags: Comb Chem High Throughput Screen Source Type: research

Facile and Efficient Synthesis of New Class of Imidazole Derivatives via one-pot Multicomponent Reactions in Water.
Abstract A water-accelerated multicomponent synthesis of organic target molecules has been used as a key method for the preparation of novel imidazole derivatives. The three-component condensation reactions of primary amines with trichloroacetonitrile in the presence of ninhydrine in water are developed as efficient and clean green synthetic procedures for the high-yielding preparation of imidazoles. PMID: 23848311 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - July 8, 2013 Category: Chemistry Authors: Hossaini Z, Seyfi S, Rostami-Charati F, Ghambarian M Tags: Comb Chem High Throughput Screen Source Type: research

Estrone Specific Molecularly Imprinted Polymeric Nanospheres: Synthesis, Characterization and Applications for Electrochemical Sensor Development.
Abstract The aim of this study is (i) to prepare estrone-imprinted nanospheres (nano-EST-MIPs) and (ii) to integrate them into the electrochemical sensor as a recognition layer. N-methacryloyl-(l)-phenylalanine (MAPA) was chosen as the complexing monomer. Firstly, estrone (EST) was complexed with MAPA and the EST-imprinted poly(2-hyroxyethylmethacrylate-co-N-methacryloyl-(l)-phenylalanine) [EST-imprinted poly(HEMA-MAPA)] nanospheres were synthesized by surfactant- free emulsion polymerization method. The specific surface area of the EST-imprinted poly(HEMA-MAPA) nanospheres was found to be 1275 m2/g with a size of...
Source: Combinatorial Chemistry and High Throughput Screening - June 28, 2013 Category: Chemistry Authors: Congur G, Senay H, Turkcan C, Canavar E, Erdem A, Akgol S Tags: Comb Chem High Throughput Screen Source Type: research

Electrochemical determination of glutathione in plasma at carbon nanotubes based screen printed electrodes.
Abstract Glutathione (GSH) is a major endogenous antioxidant highly active in human tissues and plays a key role in controlling cellular thiol redox system, maintaining the immune and detoxification system. The determination of GSH levels in tissue is important to estimate endogenous defenses against oxidative stress. In our study, the multi-walled carbon nanotube modified screen-printed electrodes (MWCNT-SPEs) were used to determine the levels of GSH in trichloroacetic acid (TCA)-treated or untreated samples of rat plasma. It was found that the deproteinization of samples with TCA improved the electrochemically d...
Source: Combinatorial Chemistry and High Throughput Screening - June 17, 2013 Category: Chemistry Authors: Turunc E, Karadeniz H, Armagan G, Erdem A, Yalcin A Tags: Comb Chem High Throughput Screen Source Type: research

Chemical Informatics and the Drug Discovery Knowledge Pyramid.
Abstract The magnitude of the challenges in preclinical drug discovery is evident in the large amount of capital invested in such efforts in pursuit of a small static number of eventually successful marketable therapeutics. An explosion in the availability of potentially drug-like compounds and chemical biology data on these molecules can provide us with the means to improve the eventual success rates for compounds being considered at the preclinical level, but only if the community is able to access available information in an efficient and meaningful way. Thus, chemical database resources are critical to any ser...
Source: Combinatorial Chemistry and High Throughput Screening - June 17, 2013 Category: Chemistry Authors: Lushington GH, Dong Y, Theertham B Tags: Comb Chem High Throughput Screen Source Type: research

A novel three-component reaction for the synthesis of 1,3-benzoxazines in water.
Abstract A simple and proficient method for the synthesis of 1,3-benzoxazine derivatives via three-component reaction of isocyanide and isoquinoline with 1-(6-hydroxy-2-isopropenyl-1-benzofuran-yl)-1-ethanone or 4-hydroxycumarine in water in the presence of piperidine at 70oC is reported. PMID: 23782038 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - June 17, 2013 Category: Chemistry Authors: Rostami-Charati F Tags: Comb Chem High Throughput Screen Source Type: research

A facile one-pot synthesis of functionalized 1,3-oxathiolan-2-yliden derivatives: Multicomponent reaction of oxiranes in water.
Abstract An efficient synthesis of 1,3-oxathiolan-2-yliden derivatives is described via a simple reactions between CH-acids, CS2 and oxiranes in the presence of triethylamine at 70°C in water as the solvent. The mild reaction conditions and high yields of the products exhibit the good synthetic advantage of this method. PMID: 23755720 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - June 10, 2013 Category: Chemistry Authors: Rostami-Charati F, Hosseini-Tabatabaei MR, Shahraki M Tags: Comb Chem High Throughput Screen Source Type: research

Solvent-Free Synthesis of Functionalized Thiazoles Using Multicomponent Reaction of Isothiocyanates.
Abstract An efficient synthesis of thiazoles is described via an one-pot reaction between acid chlorides, ammonium thiocyanate tetramethylguanidine and α-bromocarbonyl compounds under solvent-free conditions without using any catalyst. The method offers several advantages including high yields of products and an easy work-up procedure at room temperature in excellent yield. PMID: 23721069 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - May 29, 2013 Category: Chemistry Authors: Sayyed-Alangi SZ, Hossaini Z, Rostami-Charati F, Sajjadi-Ghotabadi H Tags: Comb Chem High Throughput Screen Source Type: research

Multicomponent Reactions for the Synthesis of Functionalized Imidazoles.
Abstract An efficient synthesis of functionalized tetrahydroimidazoles via a one-pot tandem reaction between ninhydrin, primary alkylamines, arylisocyanates or arylisothiocyanates, acetylenic esters and triphenylphosphine is described. PMID: 23713458 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - May 22, 2013 Category: Chemistry Authors: Seyfi S, Hossaini Z, Rostami-Charati F Tags: Comb Chem High Throughput Screen Source Type: research

Detailed Study of Precipitation of a Poorly Water Soluble Test Compound Using Methodologies as in Activity And Solubility Screening - Mixing and Automation Effects.
Abstract Storage of pharmaceutical discovery compounds dissolved in dimethylsulfoxide (DMSO) is commonplace within industry. Often, the DMSO stock solution is added to an aqueous system (e.g. in bioassay or kinetic solubility testing)- since most test compounds are hydrophobic, precipitation could occur. Little is known about the factors affecting this precipitation process at the low (μM) concentrations used in screening analyses. Here, a poorly water soluble test compound (tolnaftate) was used to compare manual and automated pipetting, and explore the effect of mixing variables on precipitation. The amount of...
Source: Combinatorial Chemistry and High Throughput Screening - May 22, 2013 Category: Chemistry Authors: Gillespie C, Kennedy AR, Edwards D, Dowden L, Daublain P, Halling P Tags: Comb Chem High Throughput Screen Source Type: research

Synthesis of Unsaturated Α-Acyloxybenzothiazoleamides Via the Passerini Three-Component Reaction.
Synthesis of Unsaturated Α-Acyloxybenzothiazoleamides Via the Passerini Three-Component Reaction. Comb Chem High Throughput Screen. 2013 May 22; Authors: Sheikholeslami-Farahani F, Shahvelayati AS Abstract 4-Benzothiazol-2-ylamino-4-oxo-2-butenoic acid, prepared from reaction of 2-aminobenzothiazole and maleic anhydride, are used as an acid component in Passerini three-component reaction, under solvent-free media, to produce unsaturated α-benzothiazole acyloxyamides in good yields. PMID: 23713460 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - May 22, 2013 Category: Chemistry Authors: Sheikholeslami-Farahani F, Shahvelayati AS Tags: Comb Chem High Throughput Screen Source Type: research

Pharmacophore Design, Virtual Screening, Molecular Docking and Optimization Approaches to Discover Potent Thrombin Inhibitors.
Abstract Thrombin plays a central role in the regulation of haemostasis and thrombosis. Inhibition of thrombin is therefore an effective therapeutic target to prevent the formation of blood clots and related thromboembolic disorders. Hence, we have developed chemical feature based pharmacophore models of thrombin inhibitors. The best hypothesis, Hypo1, characterized with two hydrogen bond acceptors (A), one hydrophobic (H) and one ring aromatic (R) feature. Hypo1 was cross validated using various techniques to prove its robustness and statistical significance. The well validated model Hypo1 was used as 3D query to...
Source: Combinatorial Chemistry and High Throughput Screening - May 22, 2013 Category: Chemistry Authors: Loganathan C, Sakkiah S, Lee KW, Kabilan S, Meganathan C Tags: Comb Chem High Throughput Screen Source Type: research

Cu(II) Schiff Base Complex as Highly Efficient Catalyst for the synthesis of Polyhydroquinoline Derivatives via Hantzsch Condensation in Water.
Abstract In the present study, we introduce Cu(II) Schiff-base complex as highly efficient and green solid catalyst for the unsymmetrical Hantzsch condensation through a four-components coupling of various aldehydes, dimedone, ethyl acetoacetate and ammonium acetate to form polyhydroquinoline derivatives in good to excellent yields. This reaction has been carried out in the presence of 1 mol% of catalysts in water at room temperature. The reusability of the catalysts was demonstrated by a five-run test. Remarkable features of this new procedure are cleaner reaction profiles, shorter reaction times, simple experim...
Source: Combinatorial Chemistry and High Throughput Screening - May 20, 2013 Category: Chemistry Authors: Vahdat SM, Golchoubian H, Mardani HR, Baghery S Tags: Comb Chem High Throughput Screen Source Type: research

High throughput screening of 7-methylpicene-1,2-diol as Arylamine N-acetyltransferase (NAT) inhibitor to establish a Isoniazid supplement in anti-tubercular therapy.
Abstract Mycobacterium tuberculosis (Mtb), due to its unusual organization crosses different immune barriers and causes tuberculosis. The advent of multidrug resistance tuberculosis (MDR-TB) has attained alarming situation. Hence, computational drug design has been performed in this work to find potent molecules for this purpose. Isoniazid is a widely used frontline drug against tuberculosis. But reports justified the inactivity of isoniazid on acetylation by Arylamine N-acetyltransferase (NAT). 35 countries were highlighted to have isoniazid resistance from survey in 1998. Hence, Mtb NAT has been selected as the ...
Source: Combinatorial Chemistry and High Throughput Screening - May 20, 2013 Category: Chemistry Authors: Chowdhury A, Paul P, Choudhury MD Tags: Comb Chem High Throughput Screen Source Type: research

Exploring Structural Requirements for a Class of Nucleoside Inhibitors (PfdUTPase) as Antimalarials: First Report on QSAR, Pharmacophore Mapping and Multiple Docking Studies.
Abstract Multi-drug resistance to the available antimalarial drugs is a major threat for malaria treatment. Due to the recent characterization of human and parasite genome sequences, both ligand and target based drug design strategies may be helpful for the design of potential antimalarial compounds with reduced degree of resistance. The present work deals with quantitative structure-activity relationship (QSAR) modeling, pharmacophore mapping and docking studies of a series of 95 nucleoside analogs as inhibitors of Plasmodium falciparum deoxyuridine-5'-triphosphate nucleotidohydrolase (PfdUTPase), an enzyme invol...
Source: Combinatorial Chemistry and High Throughput Screening - May 20, 2013 Category: Chemistry Authors: Ojha PK, Roy K Tags: Comb Chem High Throughput Screen Source Type: research

Assessment of the Integrity of Compounds Stored in Assay-ready Plates Using a Kinase Sentinel Assay.
Abstract Sentinel assays are a convenient adjunct to LC-MS purity assessment to monitor the integrity of compounds in pharmaceutical screening collections over time. To assess the stability of compounds stored both at room temperature and at -20oC in assay-ready plates that were either vacuum pack-sealed using a convenient industrial vacuum sealing method or individually sealed using conventional foil seals, a diverse collection of ~ 5,000 compounds was assayed using a robust biochemical kinase assay at intervals over a one year period. Assay results at each time point were compared to those of initial assay using...
Source: Combinatorial Chemistry and High Throughput Screening - May 6, 2013 Category: Chemistry Authors: Chen A, Zhao X, Mercer L, Su C, Zalameda L, Liu Y, Lembke A, Eastwood H, Dang S, Oung T, Xia X, Young SW, Xiao S, McCarter JD Tags: Comb Chem High Throughput Screen Source Type: research

Non-Degenerate Graphical Representation of Dna Sequences and its Applications to Phylogenetic Analysis.
Abstract In this paper, we propose a new 3-D graphical representation of a DNA sequence and prove that it has two well properties: (1) there is no circuit in the graph; (2) there exists an one-to-one correspondence between a DNA sequence and the graph. These properties guarantee it has nondegeneracy. Based on the 3-D graphical representation, we characterize a DNA sequence by a 12-dimensional vector whose components are normalized ALE-indexes of the corresponding L/L matrices. The proposed approach is tested by the phylogenetic analysis on three datasets, and the experimental assessment demonstrates its efficiency...
Source: Combinatorial Chemistry and High Throughput Screening - April 19, 2013 Category: Chemistry Authors: Yang Y, Zhang Y, Jia M, Li C, Meng L Tags: Comb Chem High Throughput Screen Source Type: research

Modeling Anti-Allergic Natural Compounds by Molecular Topology.
;n-Ortiz JV Abstract Molecular topology has been applied to the search of QSAR models able to identify the anti-allergic activity of a wide group of heterogeneous compounds. Through the linear discriminant analysis and artificial neural networks, correct classification percentages above 85% for both the training set and the test set have been obtained. After carrying out a virtual screening with a natural product library, about thirty compounds with theoretical anti-allergic activity have been selected. Among them, hesperidin, naringin, salinomycin, sorbitol, curcumol, myricitrin, diosmin and kinetin stand out. So...
Source: Combinatorial Chemistry and High Throughput Screening - April 16, 2013 Category: Chemistry Authors: García-Domenech R, Zanni R, Galvez-Llompart M, de Julián-Ortiz JV Tags: Comb Chem High Throughput Screen Source Type: research

Quantitative Structure-Activity Relationships of the Antimalarial Agent Artemisinin and some of its Derivatives - A DFT Approach.
Abstract Artemisinin form the most important class of antimalarial agents currently available, and is a unique sesquiterpene peroxide occurring as a constituent of Artemisia annua. Artemisinin is effectively used in the treatment of drug-resistant Plasmodium falciparum and because of its rapid clearance of cerebral malaria, many clinically useful semisynthetic drugs for severe and complicated malaria have been developed. However, one of the major disadvantages of using artemisinins is their poor solubility either in oil or water and therefore, in order to overcome this difficulty many derivatives of artemisinin we...
Source: Combinatorial Chemistry and High Throughput Screening - April 10, 2013 Category: Chemistry Authors: Rajkhowa S, Hussain I, Hazarika KK, Deka RC Tags: Comb Chem High Throughput Screen Source Type: research

TLC Bioautography: High-throughput Technique for Screening of Bioactive Natural Products.
Abstract TLC bioautography is a method that combines chromatographic separation and in situ biological activity determination. The antimicrobial, antioxidant and enzyme inhibitory activities can be performed on TLC bioautography. This method is mainly used for preliminary screening natural products possessing these biological activities and for the bioactivity-directed fractionation and isolation of active components from complex extracts. This review covers the mechanisms and methodology of the antimicrobial, antioxidant activities, and enzyme inhibition adopted on TLC. It will be in particular discuss the recent...
Source: Combinatorial Chemistry and High Throughput Screening - April 10, 2013 Category: Chemistry Authors: Cheng Z, Wu T Tags: Comb Chem High Throughput Screen Source Type: research

Synthesis Of 1,4,5-Trisubstituted 1,2,3-Triazoles Amicable For Automation.
Abstract A three-component 3+2 cycloaddition reaction followed by Suzuki coupling reaction were carried out to synthesize a library of compounds using automation (parallel synthesizer). Scaffolds that are unexplored in literature were used for the synthesis of library. The iodo-triazoles formed by 3+2 cycloaddition reaction were coupled with boronic acids to get tri-substituted triazoles. PMID: 23597250 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - April 10, 2013 Category: Chemistry Authors: Kavitha M, Mahipal B, Mainkar PS, Chandrasekhar S Tags: Comb Chem High Throughput Screen Source Type: research

The comparison between the calculated and HPLC-predicted lipophilicity parameters for selected groups of drugs.
Abstract The parameters of lipophilicity for three different groups of drugs (as twelve analgesics drugs, eleven cardiovascular system drugs, and thirty six compounds characterized by divergent pharmacological activity) were experimentally determined by HPLC methods as well as calculated using various computer programs (HyperChem, ACD/Labs, ChemAxon, Dragon and VCCLab). The relationships between experimental (chromatographic) parameters of lipophilicity (log k and log kw) and the chemical structure of the studied compounds, and their comparison due to the lipophilic and hydrophilic character were presented. Moreov...
Source: Combinatorial Chemistry and High Throughput Screening - April 3, 2013 Category: Chemistry Authors: Stasiak J, Koba M, Kawczak P, Bączek T, Bober L Tags: Comb Chem High Throughput Screen Source Type: research

A Green and Efficient Protocol for the Synthesis of Quinoxaline, Benzoxazole and Benzimidazole Derivatives Using Heteropolyanion-Based Ionic Liquids: as a Recyclable Solid Catalyst.
Abstract In this paper, we introduce two nonconventional ionic liquid compounds in the solid state at room temperature composed of propane sulfonate functionalized organic cations and heteropolyanions as a green solid acid catalysts for the highly efficient and green synthesis of 2,3-disubstituted quinoxaline derivatives via the one-pot condensation reaction of various o-phenylenediamine with 1,2-diketone derivatives. Benzoxazole and benzimidazole derivatives via the one-pot condensation from reaction orthoester with o-aminophenol (synthesis of benzoxazole derivatives) and o-phenylenediamine (synthesis of benzimid...
Source: Combinatorial Chemistry and High Throughput Screening - April 2, 2013 Category: Chemistry Authors: Vahdat SM, Khavarpour M, Baghery S, Kouhi ZR Tags: Comb Chem High Throughput Screen Source Type: research

High throughput screening and structure-activity relationship study of potential α2A-adrenoceptor agonists by LANCETM cAMP assay.
High throughput screening and structure-activity relationship study of potential α2A-adrenoceptor agonists by LANCETM cAMP assay. Comb Chem High Throughput Screen. 2013 Mar 18; Authors: Yang H, He L, Yan M, He JG, Yu T Abstract G protein-coupled receptors (GPCRs) are signaling molecules with a wide variety of skills. Members of this large family of membrane protein have been shown to regulate the activities of the different signaling pathways of the ligand specific manner. α2-adrenoceptors (α2-ARs) are one of the GPCRs and the stimulation of them could modulate many classical effects such...
Source: Combinatorial Chemistry and High Throughput Screening - March 18, 2013 Category: Chemistry Authors: Yang H, He L, Yan M, He JG, Yu T Tags: Comb Chem High Throughput Screen Source Type: research