Cytotoxic Tumor-Targeting Peptides From In Vivo Phage Display.
Abstract We previously utilized an in vivo peptide phage display selection technique, which included the use of detergent elution of phage from excised tumor, to obtain tumor-targeting phage with the ability to extravasate the vasculature and bind directly to prostate tumor tissue. It is hypothesized that this same in vivo phage selection technique can be used to functionally select for molecules that not only bind to cancer cells but also kill them. Here we analyzed two different in vivo phage display selected phage clones, G1 and H5, retrieved from PC-3 human prostate carcinoma xenografted tumors. First, cell de...
Source: Combinatorial Chemistry and High Throughput Screening - April 8, 2016 Category: Chemistry Authors: Northup JR, Deutscher SL Tags: Comb Chem High Throughput Screen Source Type: research

Red-fluorescent Activatable Probes for the Detection of Hydrogen Peroxide in Living Cells.
Abstract Many inflammatory processes are associated with an increase in the production of reactive oxygen species (ROS). Chemical probes that specifically detect ROS are potentially useful tools for the early diagnosis of inflammatory diseases as well as cancer. Herein we have developed a library of coumarin hybrids by condensation of various heterocyclic quaternary salts to a 7-hydroxycoumarin scaffold. From our library we identified one benzothiazole-coumarin hybrid as a red-fluorescent compound with emission maxima around 620 nm and a strong fluorogenic response. Furthermore, we proved that this scaffold is sui...
Source: Combinatorial Chemistry and High Throughput Screening - April 8, 2016 Category: Chemistry Authors: Garcia-Guzman C, Fernandez A, Avlonitis N, Bradley M, Vendrell M Tags: Comb Chem High Throughput Screen Source Type: research

Fluorescent Formazans and Tetrazolium Salts - Towards Fluorescent Cytotoxicity Assays.
Abstract Formazan-based colorimetric cytotoxicity assays, such as the MTT assay, are typically used to assess cell viability with only metabolically active cells reducing tetrazolium salts into the formazans, which is then quantified by absorbance. Fluorescence offers several advantages compared to colorimetric assays and would enable techniques such as flow cytometry and confocal microscopy to be used for analysis. Here, fluorescent formazans 10, 11 and 12, and their corresponding tetrazolium salts 13, 16 and 24, respectively, were synthesised by incorporation of a known fluorophore backbone (coumarin, fluorescei...
Source: Combinatorial Chemistry and High Throughput Screening - April 8, 2016 Category: Chemistry Authors: Ladyman MK, Walton JG, Lilienkampf A, Bradley M Tags: Comb Chem High Throughput Screen Source Type: research

An analysis of the practicalities of multi-color nanoparticle cellular bar-coding.
Abstract Many applications in biomedical research require the long-term identification and tracking of cells over time. In previous work we have demonstrated that by sequentially dosing a cell population with different emission wavelength nanoparticles it is possible to use the random number of nanoparticle loaded vesicles generated by the cells as a barcode for individual cells within the population. In this paper we develop a simple model to describe the number of codes that can be generated using this sequential loading protocol. The methodology is validated by comparison with experiment and subsequently used t...
Source: Combinatorial Chemistry and High Throughput Screening - April 8, 2016 Category: Chemistry Authors: Rees P, Rowan Brown M, Wills JW, Summers H Tags: Comb Chem High Throughput Screen Source Type: research

Prediction of intracellular localization of fluorescent dyes using QSAR models.
E, Chang YT Abstract Control of fluorescent dye localisation in live cells is crucial for fluorescence imaging. Here, we describe quantitative structure activity relation (QSAR) models for predicting intracellular localisation of fluorescent dyes. For generating the QSAR models, electric charge (Z) calculated by pKa, conjugated bond number (CBN), the largest conjugated fragment (LCF), molecular weight (MW) and log P were used as parameters. We identified the intracellular localisation of 119 BODIPY dyes in live NIH3T3 cells, and assessed the accuracy of our models by comparing their predictions with the observed d...
Source: Combinatorial Chemistry and High Throughput Screening - April 8, 2016 Category: Chemistry Authors: Uchinomiya S, Horobin RW, Alvarado-Martínez E, Peña-Cabrera E, Chang YT Tags: Comb Chem High Throughput Screen Source Type: research

Novel biosensor of membrane protein proximity based on fluorogen activated proteins.
We describe a novel biosensor system for reporting proximity between cell surface proteins in live cultured cells. The biosensor takes advantage of recently developed fluorogen-activating proteins (FAPs) that display fluorescence only when bound to otherwise-nonfluorescent fluorogen molecules. To demonstrate feasibility for the approach, two recombinant rapamycin-binding proteins were expressed as single-pass plasma membrane proteins in HeLa cells; one of the proteins (scAvd-FRB) carried an extracellular avidin tag; the other (HL1-TO1-FKBP) carried an extracellular FAP. Cells were incubated with a membrane-impermeable biva...
Source: Combinatorial Chemistry and High Throughput Screening - April 8, 2016 Category: Chemistry Authors: Vasilev KV, Gallo E, Shank N, Jarvik JW Tags: Comb Chem High Throughput Screen Source Type: research

Combinatorial dansyl library and its applications to pH-responsive probes.
Abstract Herein, we report the first 48-membered, dansyl-based, combinatorial fluorescent library. From the electronic and structural properties of the probes, we analyzed their optical properties and chemical yields, with an average of 49 %. The molecules were examined for their pH responses, and DS-2 and DS-45 showed blue-shifts, whereas DS-7 and DS-40 showed red-shifts in wavelength with increasing pH. Finally, cell permeability was investigated by treating SNU-2292 cells. Our results demonstrate the potential application of this library in biosensors, bio-imaging and pH indicators. PMID: 27055754 [PubMed ...
Source: Combinatorial Chemistry and High Throughput Screening - April 8, 2016 Category: Chemistry Authors: Hong SC, Murale DP, Lee JS Tags: Comb Chem High Throughput Screen Source Type: research

Editorial: Validate and Verify: Keys to Scientific Excellence.
PMID: 27017823 [PubMed - in process] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - March 29, 2016 Category: Chemistry Authors: Chaguturu R, Lushington GH Tags: Comb Chem High Throughput Screen Source Type: research

Molecular Docking, Metal substitution and Hydrolysis reaction of Chiral Substrates of Phosphotriesterase.
Abstract During World War II, organophosphorus compounds with neurotoxic action were developed and used as the basis for the development of structures currently used as pesticides in the agricultural industry. Among the nerve agents, Tabun, Sarin, Soman and VX are the most important. The factor responsible for the high toxicity of organophosphorus (OP) is the acetylcholinesterase inhibition. However, one of the characterized enzymes capable of degrading OP is Phosphotriesterase (PTE). This enzyme has generated considerable interest for applications of rapid and complete detoxification. Due to the importance of bio...
Source: Combinatorial Chemistry and High Throughput Screening - March 25, 2016 Category: Chemistry Authors: de Castro AA, Caetano MS, Silva TC, Mancini DT, da Rocha EP, da Cunha EF, Ramalho TC Tags: Comb Chem High Throughput Screen Source Type: research

Identification of Protein Palmitoylation Inhibitors from a Scaffold Ranking Library.
This report describes a mixture based screening approach to identify inhibitors of Erf2 activity. Erf2 is the Saccharomyces cerevisiae PAT responsible for catalyzing the palmitoylation of Ras2, an ortholog of the human Ras oncogene proteins. A chemical library developed by the Torrey Pines Institute for Molecular Studies consists of more than 30 million compounds designed around 68 molecular scaffolds that are systematically arranged into positional scanning and scaffold ranking formats. We have used this approach to identify and characterize several scaffold backbones and R-groups that reduce or eliminate the activity of ...
Source: Combinatorial Chemistry and High Throughput Screening - March 24, 2016 Category: Chemistry Authors: Hamel LD, Lenhart BJ, Mitchell DA, Santos RG, Giulianotti MA, Deschenes RJ Tags: Comb Chem High Throughput Screen Source Type: research

Classification of Human Pregnane x Receptor (hPXR) activators and non-activators by Machine learning techniques: A multifaceted Approach.
In this study, we developed and validated the computational prediction models to classify hPXR activators and non-activators. We employed four machine learning methods, support vector machine (SVM), k-nearest neighbour (k-NN), random forest (RF) and naïve bayesian (NB). These methods were used to develop molecular and fingerprint based descriptors for the prediction of hPXR activators and non-activators. Total 529 molecules consitsting of 317 activators and 212 non-activators were used for model development. The overall prediction accuracy of models was 69% to 99% to classify hPXR activators and non-activators. In cas...
Source: Combinatorial Chemistry and High Throughput Screening - March 16, 2016 Category: Chemistry Authors: Rathod V, Belekar V, Garg P, Sangamwar AT Tags: Comb Chem High Throughput Screen Source Type: research

Characterization of seven new polystyrene plates binding peptides from a phage-displayed random 12-peptide library.
Abstract A random 12-peptide library was screened against Erysipelothrix rhusiopthiae and porcine circovirus 2 recombinant Cap protein and the selected peptides were used for detecting the corresponding pathogens quickly and effectively. To our surprise, seven peptides, P1 (WHWNAPWWNGVY), P2 (FHWTWQFPYTST), P3 (GAMHLPWHMGTL), P4 (HWNIWWQHHPSP), P5 (HFFKWHTRTNDQ), P6 (HFFRWHPSAHLG) and P7 (HFAYWWNGVRGP) with the characteristics of polystyrene plate (PS) binding target-unrelated peptides (TUPs), were selected from the library. It is found that P2 and P4 shared common motif of plastic binding peptide, moreover, P2, P...
Source: Combinatorial Chemistry and High Throughput Screening - March 16, 2016 Category: Chemistry Authors: Hu YF, Gao XC, Xu TQ, Dun Z, Yu XL Tags: Comb Chem High Throughput Screen Source Type: research

TiO2-SO42- Catalyzed Synthesis and Antimicrobial Activity / Molecular Docking Studies of β-Indolylnitroalkanes.
TiO2-SO42- Catalyzed Synthesis and Antimicrobial Activity / Molecular Docking Studies of β-Indolylnitroalkanes. Comb Chem High Throughput Screen. 2016 Mar 15; Authors: Santhisudha S, Jayaprakash SH, Mohan G, Kumar YN, Suganthi V, Mohanasrinivasan V, Reddy CS Abstract Michael addition of indole derivatives with various substituted nitrostyrenes to yield β-indolylnitroalkanes is accomplished effectively under solvent free conditions using TiO2-SO42- as efficient catalyst at 60 º C. All the synthesized compounds were screened for their antibacterial activity through in silico and in vitro ...
Source: Combinatorial Chemistry and High Throughput Screening - March 15, 2016 Category: Chemistry Authors: Santhisudha S, Jayaprakash SH, Mohan G, Kumar YN, Suganthi V, Mohanasrinivasan V, Reddy CS Tags: Comb Chem High Throughput Screen Source Type: research

Facial and Efficient Access to Dihydropyrano[3,2-c]chromenes via Three-Component Reaction Using N,N-Dimethylbenzylamine As a New Organocatalyst.
Abstract The N,N-dimethylbenzylamine (DMBA), as an efficient and commercially available organocatalyst was employed for the one-pot synthesis of dihydropyrano[3,2-c]chromene derivatives in ethanol medium. In this work, the one-pot Knoevenagel-Michael-Thorpe-Ziegler type cascade heterocyclization has been developed for the synthesis of dihydropyrano[3,2-c]chromene-containing heterocycles from the one-pot multicomponent condensation reaction of 4-hydroxycoumarin, malononitrile/ethyl cyanoacetate, and various aldehydes at 60 °C. The salient features of this base-catalyzed reaction are mild reaction conditions, re...
Source: Combinatorial Chemistry and High Throughput Screening - March 10, 2016 Category: Chemistry Authors: Kiyani H, Jalali M Tags: Comb Chem High Throughput Screen Source Type: research

Properties of ultraviolet exposed camptothecin studied by using optical spectroscopy methods.
Abstract Camptothecin (CPT) and its analogs as inhibitors of topoisomerase I are anticancer compounds. Their antitumor potency is seriously limited due to hydrolysis of lactone form of camptothecins in solutions at pH>5.5, which leads to the formation of inactive carboxylate form with open lactone ring. Furthermore, the clinical application of CPT is also restricted by strong affinity of its carboxylate form to human serum albumin which destabilizes the active lactone form. By UV irradiation of the CPT carboxylate authors of this paper received camptothecin compound which has biophysical properties similar to t...
Source: Combinatorial Chemistry and High Throughput Screening - March 8, 2016 Category: Chemistry Authors: Ziomkowska B, Wybranowski T, Cyrankiewicz M, Kruszewski S Tags: Comb Chem High Throughput Screen Source Type: research

Fragment-based de novo design of antimycobacterial agents and in vitro potency evaluation.
Abstract Tuberculosis (TB) is an infection with global impact that over time demonstrates enormously high mortality rates. The vital need for improving novel and efficient anti-TB drugs is caused by the rising rate of appearance of Multi Drug Resistant (MDR) strains to the frequently utilized drugs.In addition, the longer periods of therapy and healing, mainly in the immune compromised patients aggrevates the situation. Recent studies indicates that computer-based techniques have been used successfully in the antibacterial research. In our current approach, utilizing combined pattern of computer-based methods as f...
Source: Combinatorial Chemistry and High Throughput Screening - February 18, 2016 Category: Chemistry Authors: Sardari S, Portugal I, ALKafri A, Moradi D, Ghavami G Tags: Comb Chem High Throughput Screen Source Type: research

Insights from analysis of binding sitesof human meprins: Screening of inhibitors by molecular dynamics simulation study.
Abstract Human meprin-α and-β are important regulators of angiogenesis, cancer, inflammation, fibrosis, and neurodegenerative diseases and hence important therapeutic targets. Meprins are the only astacin proteases that are expressed in membrane-bound and secreted form. The cleavage specificity of human meprins is similar in certain cases but differs markedly in others. The inhibitor selectivity of human meprins is controlled by the specific residues involved in binding at the active-site cleft of the proteases. Meprins are inhibited by various small molecular inhibitors as well as macromolecular endoge...
Source: Combinatorial Chemistry and High Throughput Screening - February 15, 2016 Category: Chemistry Authors: Chaudhuri A, Bera AK, Sarkar I, Chakraborty S Tags: Comb Chem High Throughput Screen Source Type: research

High Throughput Screening for Colorectal Cancer Specific Compounds.
Abstract The development of new anti-cancer therapeutic agents is necessary to improve antitumor efficacy and reduce toxicities. Here we report using a systematic anticancer drug screening approach we developed previously, to concurrently screen colon and glioma cancer cell lines for 2000 compounds with known bioactivity and 1920 compounds with unknown activity. The hits specific to each tumor cell line were then selected, and further tested with the same cells transfected with EGFP (Enhanced Green Fluorescent Protein) alone. By comparing the percentage of signal reduction from the same cells transfected with the ...
Source: Combinatorial Chemistry and High Throughput Screening - February 2, 2016 Category: Chemistry Authors: Xie J, Wang C, Gore JC Tags: Comb Chem High Throughput Screen Source Type: research

An Efficient Four-Step Approach toward Fused Triazino[1,6-a]Quinazolines.
Abstract Herein, we describe a simple, four-step process for the preparation of 1,2,3-triazino[1,6-a]quinazolin-13-ones. This method involves ring-opening, quinazoline-forming condensation, reduction, diazotization accompanied by rapid intramolecular cyclization in the last step afforded the desired products with structurally complex heterocyclic core in excellent to high yields. PMID: 26830360 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - February 2, 2016 Category: Chemistry Authors: Sayahi MH, Baghersaei S, Goli F, Moghimi S, Mahdavi M, Firoozpour L, Shafiee A, Foroumadi A Tags: Comb Chem High Throughput Screen Source Type: research

Editorial: Investigate the Functions of Chemicals Through Heterogeneous Network of Chemicals and Proteins.
PMID: 26805436 [PubMed - in process] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - January 26, 2016 Category: Chemistry Authors: Cai YD Tags: Comb Chem High Throughput Screen Source Type: research

Synthesis and Antifeedant Activities of Rosin-based Esters against Armyworm.
Abstract A series of rosin based esters have been synthesized from dehydroabietic acid and maleopimaric acid, respectively. Their structures were confirmed by FT-IR, 1H NMR, 13C NMR and single crystal X-ray diffraction. Their antifeedant activities against armyworm were examined by leaf plate method. Methyl ester of dehydroabietic acid and maleopimaric acid crystallized in orthorhombic system with cell dimensions of a = 26.352 (5) Å, b = 6.1020 (12) Å, c = 11.812 (2) Å and a = 7.9216(11)Å, b = 11.9912(16)Å, c = 23.425(3)Å, respectively, they contained classic tricycl...
Source: Combinatorial Chemistry and High Throughput Screening - January 20, 2016 Category: Chemistry Authors: Li L, Xinyan Y, Yanqing G, Xiao-Ping R Tags: Comb Chem High Throughput Screen Source Type: research

Editorial: A Look Back at 2015: Hope, Hype and Hypocrisy.
PMID: 26743190 [PubMed - in process] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - January 15, 2016 Category: Chemistry Authors: Chaguturu R Tags: Comb Chem High Throughput Screen Source Type: research

A Theoretical Study on Stepwise- and Concertedness of The Mechanism of 1,3-Dipolar Cycloaddition Reaction between Tetra Amino Ethylene and Trifluoro Methyl Azide.
Abstract The order of reaction, especially in 1,3-dipolar cycloadditions directly affects the products' stereo selectivity. Due to this fact that a wide range of heterocyclic rings of natural products and biologically active molecules are synthesizing via this valuable procedure, understanding about the order of this reaction is so useful in designing the synthesis of different types of heterocyclic species. Therefore, the order of 1, 3-dipolar reaction has been carefully studied by many researchers but it seems that this question is still open despite many valuable answers. Considering this, in the present work, ...
Source: Combinatorial Chemistry and High Throughput Screening - December 16, 2015 Category: Chemistry Authors: Siadati SA Tags: Comb Chem High Throughput Screen Source Type: research

Pharmacophore-based 3D-QSAR modeling, Virtual Screening and Molecular Docking Analysis for the Detection of MERTK Inhibitors with Novel Scaffold.
In this study, 107 MERTK inhibitors with known activities were gathered to generate a ligand-based pharmacophore model (ADDHH.4), followed by building a 3D-QSAR model, which had high value of coefficient of determination (R2=0.9061) and high value of coefficient of determination (Q2=0.7442). For the pharmacophore model, two hydrogen bond donors (D), one hydrogen bond receptor (A), and two hydrophobic groups (H) were considered as the key elements contributing to ligand activity. The model then served to search a drug-like database with 1.5 million molecules, and 47832 hits were obtained. Subsequently, docking procedure was...
Source: Combinatorial Chemistry and High Throughput Screening - December 16, 2015 Category: Chemistry Authors: Zhou S, Zhou L, Cui R, Tian Y, Li X, You R, Zhong L Tags: Comb Chem High Throughput Screen Source Type: research

An In Silico Approach for Identification of Potential Anti-Mycobacterial Targets of Vasicine and Related Chemical Compounds.
Abstract Tuberculosis (TB) is known to mankind as one of the most pervasive and persistent of diseases since the early days of civilization. The growing resistance of the causative pathogen Mycobacterium tuberculosis to the standard drug regimen for TB poses further difficulty in its treatment and control. Screening of novel plant-derived compounds with promising anti-tubercular activity has been cited as a prospective route for new anti-tubercular drug discovery and design. Justicia adhatoda L. is a perennial evergreen shrub which is widely mentioned in scientific literature on account of its potent anti-mycobact...
Source: Combinatorial Chemistry and High Throughput Screening - December 2, 2015 Category: Chemistry Authors: Chaliha AK, Gogoi D, Chetia P, Sarma D, Kumar Buragohain A Tags: Comb Chem High Throughput Screen Source Type: research

An Integrated in Silico Method to Discover Novel Rock1 Inhibitors: Multi-Complex-Based Pharmacophore, Molecular Dynamics Simulation and Hybrid Protocol Virtual Screening.
Abstract Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) is an important regulator of focal adhesion, actomyosin contraction and cell motility. In this manuscript, a combination of the multi-complex-based pharmacophore (MCBP), molecular dynamics simulation and a hybrid protocol of a virtual screening method, comprised of multi-pharmacophore-based virtual screening (PBVS) and ensemble docking-based virtual screening (DBVS) methods were used for retrieving novel ROCK1 inhibitors from the natural products database embedded in the ZINC database. Ten hit compounds were selected from the hit compounds, a...
Source: Combinatorial Chemistry and High Throughput Screening - December 2, 2015 Category: Chemistry Authors: Chen H, Li S, Hu Y, Cai L, Jiang Q, Tong R, Zang Z, Chen G Tags: Comb Chem High Throughput Screen Source Type: research

Bioactivity-Guided Isolation of Antiproliferative Sesquiterpene Lactones from Centaurea Solstitialis L. ssp. Solstitialis.
Abstract Centaurea solstitialis L. ssp. solstitialis (CSS) has been used as medicine for various diseases. In this work; root, stem and flower parts of the plant were separately extracted with methanol to execute bioassay-guided isolation. Antiproliferative activities of each extracts on C6 cells (Rat Brain tumor cells) and HeLa cells (human uterus carcinoma) were investigated in vitro. The methanol extract of stem exhibited the most antiproliferative activity therefore isolation of active compounds was carried out for stem of the plant. Methanol extract of stem was boiled at 97 °C for 2 hours in water then ex...
Source: Combinatorial Chemistry and High Throughput Screening - December 2, 2015 Category: Chemistry Authors: Erenler R, Sen O, Sahin Yaglioglu A, Demirtas I Tags: Comb Chem High Throughput Screen Source Type: research

Pharmacophore-based 3D-QSAR modeling, Virtual Screening and Molecular Docking Analysis for Detection of MERTK Inhibitors with Novel Scaffold.
In this study, 107 MERTK inhibitors with known activities were gathered to generate a ligand-based pharmacophore model (ADDHH.4), followed by building a 3D-QSAR, which had high value of coefficient of determination (R2=0.9061) and high value of coefficient of determination (Q2=0.7442). For the pharmacophore model, two hydrogen bond donors (D), one hydrogen bond receptor (A), and two hydrophobic groups (H) were considered as the key elements contributing to the ligand activity. The model then served to search a drug-like database with 1.5 million molecules, and 47832 hits returned. Subsequently, docking procedure was put on...
Source: Combinatorial Chemistry and High Throughput Screening - December 2, 2015 Category: Chemistry Authors: Zhou S, Zhou L, Tian Y, Li X, You R, Zhong L Tags: Comb Chem High Throughput Screen Source Type: research

Thiazole-Based Thiazolidinones as Potent Antimicrobial Agents. Design, Synthesis and Biological Evaluation.
Abstract As a part of our ongoing project on design and synthesis of new thiazole derivatives with antimicrobial activity fourteen new ethyl 2-(2-((E)-((Z)-5-(4-benzyliden)-4-oxothiazolidin-2-yliden)amino-4-yl)acetates , carrying halogens, methoxy and other groups were synthesized. Compounds were tested against eight Gram positive and negative bacteria as well as eight yeasts and mold by microdilution assay. All compounds showed good activity against all bacteria tested with MIC ranging between 2.3-39.8 μmol/ml x 10-2 and MBC of 9.2-79.6 μmol/ml x 10-2. As reference drugs Ampicillin (MIC 24.8-74.4 and MBC 37...
Source: Combinatorial Chemistry and High Throughput Screening - December 2, 2015 Category: Chemistry Authors: M H, C T, E T, A G Tags: Comb Chem High Throughput Screen Source Type: research

Efficient Isothermal Titration Calorimetry Technique Identifies Direct Interaction of Small Molecule Inhibitors with the Target Protein.
In this study we applied this strategy in a search for a small molecule capable of interfering with the interaction of the tumor-suppressor p53 and the E3-ligase MDM2. We virtually screened a library of 15 million small molecules that were filtered to a final set of 80 virtual hits. Our in vitro experimental assay, designed to validate the activity of mixtures of compounds by isothermal titration calorimetry, was used to identify an active molecule against MDM2. At the end of the process the small molecule (4S,7R)-4-(4-chlorophenyl)-5-hydroxy-2,7-dimethyl-N-(6-methylpyridin-2-yl)-4,6,7,8 tetrahydrIoquinoline-3-carboxamide ...
Source: Combinatorial Chemistry and High Throughput Screening - December 2, 2015 Category: Chemistry Authors: Gal M, Bloch I, Shechter N, Romanenko O, M Shir O Tags: Comb Chem High Throughput Screen Source Type: research

Editorial: Recent Trends and Advancements in Bioassay Based on Bioluminescent Technologies.
PMID: 26552481 [PubMed - in process] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - November 13, 2015 Category: Chemistry Authors: Frank LA Tags: Comb Chem High Throughput Screen Source Type: research

High Throughput Screening of Esterases, Lipases and Phospholipases in Mutant and Metagenomic Libraries: A Review.
eyes-Duarte D, Ferrer M Abstract Nowadays, enzymes can be efficiently identified and screened from metagenomic resources or mutant libraries. A set of a few hundred new enzymes can be found using a simple substrate within few months. Hence, the establishment of an enzymes collection is no longer a big hurdle. However, a key problem is the relatively low rate of positive hits and that a timeline of several years from the identification of a gene to the development of a process is the reality rather than the exception. Major problems are related to the time-consuming and cost-intensive screening process that only ve...
Source: Combinatorial Chemistry and High Throughput Screening - November 10, 2015 Category: Chemistry Authors: Peña-García C, Martínez-Martínez M, Reyes-Duarte D, Ferrer M Tags: Comb Chem High Throughput Screen Source Type: research

From Classical to High Throughput Screening Methods for Feruloyl Esterases: A Review.
f-Torres A, Mateos-Díaz JC Abstract Feruloyl esterases (FAEs) are a diverse group of hydrolases widely distributed in plants and microorganisms which catalyzes the cleavage and formation of ester bonds between plant cell wall polysaccharides and phenolic acids. FAEs have gained importance in biofuel, medicine and food industries due to their capability of acting on a large range of substrates for cleaving ester bonds and synthesizing high-added value molecules through esterification and transesterification reactions. During the past two decades extensive studies have been carried out on the production, char...
Source: Combinatorial Chemistry and High Throughput Screening - November 10, 2015 Category: Chemistry Authors: Ramírez-Velasco L, Armendáriz-Ruiz M, Rodríguez-González JA, Müller-Santos M, Asaff-Torres A, Mateos-Díaz JC Tags: Comb Chem High Throughput Screen Source Type: research

Proteases and their inhibitors: from basic to high-throughput screening.
Abstract Proteases constitute one of the most important groups of industrial enzymes with a worldwide value expected to reach 2.7 billion US dollars by 2019. Proteases represent a group of enzymes that hydrolyze the peptide bonds of proteins, releasing polypeptides or free amino acids. These enzymes are used in cleaning products, production of leathers, textiles, food and dairy products, in the pharmaceutical and diagnostic industries and for water treatment. Another area of interest regarding proteases is the development of drugs that act as protease inhibitors. This review will briefly describe the general metho...
Source: Combinatorial Chemistry and High Throughput Screening - November 10, 2015 Category: Chemistry Authors: Casas-Godoy L, Sandoval G Tags: Comb Chem High Throughput Screen Source Type: research

Prediction of bioactive compound pathways using chemical interaction and structural information.
In this study, we investigated the bioactive compounds reported in Selleckchem, which were assigned to 22 pathways. A computational method was proposed to identify the pathways of the bioactive compounds. Unlike most existing methods that only consider compound structural information, the proposed method adopted both the structural and interaction information from the compounds. The total accuracy achieved by our method was 61.79% based on jackknife analysis of a dataset of 1,832 bioactive compounds. Its performance was quite good compared with that of other machine learning algorithms (with total accuracies less than 46%)...
Source: Combinatorial Chemistry and High Throughput Screening - November 10, 2015 Category: Chemistry Authors: Cheng S, Zhu C, Chu C, Huang T, Kong X, Zhu L Tags: Comb Chem High Throughput Screen Source Type: research

Analysis of the relationship between PM2.5 and lung cancer based on protein-protein interactions.
This study constitutes the analysis of the association between PM2.5 and lung cancer. Genes related to small/nonsmall cell lung cancer were evaluated by assigning scores to measure the impact caused by PM2.5. Analyses of small/nonsmall cell lung cancer genes with high scores revealed that it is theoretically possible that PM2.5 is an etiologic factor for lung cancer. Our results provided new insights of the relationship between lung cancers and air pollution. PMID: 26552437 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - November 10, 2015 Category: Chemistry Authors: Shu Y, Zhu L, Yuan F, Kong X, Huang T, Cai YD Tags: Comb Chem High Throughput Screen Source Type: research

Large-Scale Prediction of Drug Targets Based on Local and Global Consistency of Chemical-Chemical Networks.
Abstract It is crucial to identify the molecular targets of a compound during the course of the new drug discovery and drug development. Due to the complexity of biological systems, finding drug targets by biological experiments is very tedious and expensive. In the paper, we used chemical-chemical interactions in the STITCH database to construct a network of drug-drug association. Based on the network, a learning method keeping local and global consistency was presented to infer drug targets. We achieved an accuracy of 57.75% in the first order prediction using leave-one-out cross validation, which was higher tha...
Source: Combinatorial Chemistry and High Throughput Screening - November 10, 2015 Category: Chemistry Authors: Huang G, Feng K, Li X, Peng Y Tags: Comb Chem High Throughput Screen Source Type: research

Study of drug-drug combinations based on molecular descriptors and physicochemical properties.
Abstract In the present study, molecular descriptors and physicochemical properties were used to encode drug molecules. Based on this molecular representation method, Random forest was applied to construct a drug-drug combination network. After feature selection, an optimal features subset was built, which described the main factors of drugs in our prediction. As a result, the selected features can be clustered into three categories: elemental analysis, chemistry, and geometric features. And all of the three types features are essential elements of the drug-drug combination network. The final prediction model achi...
Source: Combinatorial Chemistry and High Throughput Screening - November 10, 2015 Category: Chemistry Authors: Niu B, Xing Z, Zhao M, Huo H, Huang G, Chen F, Su Q, Lu Y, Wang M, Yang J, Chen L, Tang L, Zheng L Tags: Comb Chem High Throughput Screen Source Type: research

A novel machine learning method for cytokine-receptor interaction prediction.
In this study, we propose a novel machine learning based method for cytokine-receptor interaction prediction. In the proposed method, a protein sequence is first transformed by incorporating the sequence evolutional information and then formulated by the following three aspects: (1) the k-skip-n-gram model, (2) physicochemical properties, and (3) local pseudo position-specific score matrix (local PsePSSM). Afterwards, Random Forest (RF) classifier is employed to make the predictions for potential cytokine-receptor interactions. Experimental results on a dataset from Homo sapiens show that the proposed method performs remar...
Source: Combinatorial Chemistry and High Throughput Screening - November 10, 2015 Category: Chemistry Authors: Wei L, Zou Q, Liao M, Lu H, Zhao Y Tags: Comb Chem High Throughput Screen Source Type: research

Predicting the types of metabolic pathway of compounds using molecular fragments and sequential minimal optimization.
In this study, compounds are first represented by molecular fragments which are then delivered to a prediction engine called Sequential Minimal Optimization (SMO) for predictions. Maximum relevance and minimum redundancy (mRMR) and incremental feature selection are adopted to extract key features based on which an optimal prediction engine is established. The proposed method is effective comparing to the random forest, Dagging and a popular method that integrating chemical-chemical interactions and chemical-chemical similarities. We also make predictions using some compounds with unknown metabolic pathways and choose 17 co...
Source: Combinatorial Chemistry and High Throughput Screening - November 10, 2015 Category: Chemistry Authors: Chen L, Chu C, Feng K Tags: Comb Chem High Throughput Screen Source Type: research

Analysis of A Drug Target-based Classification System using Molecular Descriptors.
In this study, we gave an investigation on five target-based classes: (I) G protein-coupled receptors; (II) Nuclear receptors; (III) Ion channels; (IV) Enzymes; (V) Pathogens, using molecular descriptors to represent each drug compounds. Two popular feature selection methods, maximum relevance minimum redundancy and incremental feature selection, were adopted to extract the important descriptors. Meanwhile, an optimal prediction model based on nearest neighbor algorithm was constructed, which got the best result in identifying drug target-based classes. Finally, some key descriptors were discussed to uncover their importan...
Source: Combinatorial Chemistry and High Throughput Screening - November 10, 2015 Category: Chemistry Authors: Lu J, Zhang P, Bi Y, Luo X Tags: Comb Chem High Throughput Screen Source Type: research

Are Topological Properties of Drug Targets Based on Protein-Protein Interaction Network Ready to Predict Potential Drug Targets?
In this study, three levels of verification strategies were designed and conducted by applying support vector machine (SVM) as the classification tool. Unfortunately, none of the models built was capable to get the accuracy better than 80%, and most of the performances were between 0.6-0.7 for the area under the curve (AUC). Hence, conclusion was proposed that topological properties of drug targets are not prepared to predict potential drug targets based on the present PPIN. This summary was also underpinned by the unsatisfying prediction data reported by other investigators. Finally, data quality and quantity of the prote...
Source: Combinatorial Chemistry and High Throughput Screening - November 10, 2015 Category: Chemistry Authors: Li S, Yu X, Zou C, Gong J, Liu X, Li H Tags: Comb Chem High Throughput Screen Source Type: research

Antioxidant capacity determination of complex samples and individual phenolics - Multilateral approach.
Abstract Antioxidant (AO) capacity of various medicinal plants extracts and phenolic compounds was assessed by the most widely used spectrophotometric assays such as ferric reducing antioxidant power (FRAP), scavenging of 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH). In addition, two direct current (DC) polarographic assays, one based on decrease of anodic current of HydroxoPerhydroxoMercury(II) complex (HPMC) formation in alkaline solution of H2O2, at potential of mercury dissolution and another recently developed Mercury Reduction Antioxidant Power (MRAP), ...
Source: Combinatorial Chemistry and High Throughput Screening - November 1, 2015 Category: Chemistry Authors: Petrović M, Sužnjević D, Pastor F, Veljović M, Pezo L, Antić M, Gorjanović S Tags: Comb Chem High Throughput Screen Source Type: research

A Rapid Python-Based Methodology for Target-Focused Combinatorial Library Design.
Abstract The chemical space is so vast that only a small portion of it has been examined. As a complementary approach to systematically probe the chemical space, virtual combinatorial library design has extended enormous impacts on generating novel and diverse structures for drug discovery. Despite the favorable contributions, high attrition rates in drug development that mainly resulted from lack of efficacy and side effects make it increasingly challenging to discover good chemical starting points. In most cases, focused libraries, which are restricted to particular regions of the chemical space, are deftly expl...
Source: Combinatorial Chemistry and High Throughput Screening - November 1, 2015 Category: Chemistry Authors: Li S, Song Y, Liu X, Li H Tags: Comb Chem High Throughput Screen Source Type: research

Network pharmacology of Ayurveda formulation Triphala with special reference to anti-cancer property.
Abstract Network pharmacology is an emerging technique, which integrates systems biology and computational biology to study multi-component and multi-targeted formulations. Ayurveda, the traditional system of Indian medicine, uses intelligent formulations; however, their scientific rationale and mechanisms remain largely unexplored. This paper presents the potential of network pharmacology to understand the rationale of a commonly used Ayurveda formulation known as Triphala. We have developed pharmacology networks of Triphala based on the information gathered from different databases and using the software Cytosca...
Source: Combinatorial Chemistry and High Throughput Screening - October 18, 2015 Category: Chemistry Authors: Chandran U, Mehendale N, Tillu G, Patwardhan B Tags: Comb Chem High Throughput Screen Source Type: research

Establishment of a Primary Screening Assay for the DHX9 Helicase.
Pelletier J Abstract The RNA helicase DHX9 is an ATP-dependent DExH box helicase that can unwind DNA and RNA. Much evidence has implicated DHX9 at multiple levels of gene expression regulation ranging from genome stability and replication, to transcriptional control and translation regulation. Its association with the EWS-FLI1 fusion product, as well as the finding that its suppression can be synthetic lethal with the BCL-2 family inhibitor ABT-737 indicates a potential role in tumor maintenance. Hence, to identify small molecules that could interfere with its activity, we developed a homogenous RNA-dependent ATPa...
Source: Combinatorial Chemistry and High Throughput Screening - October 18, 2015 Category: Chemistry Authors: Cencic R, Sénéchal P, Pelletier J Tags: Comb Chem High Throughput Screen Source Type: research

Applications of luminous bacteria enzymes in toxicology.
Abstract This review describes the principle and applications of bioluminescent enzymatic toxicity bioassays. This type of assays uses bacterial coupled enzyme systems: NADH:FMN-oxidoreductase and luciferase to replace living organisms in developing cost-competitive biosensors for environmental, medical and industrial applications. These biosensors instantly signal chemical and biological hazards and allow for detecting a great amount of toxic compounds with advantages associated with fast results, high sensitivity, simplicity, low cost and safety of the procedure. PMID: 26377542 [PubMed - as supplied by publ...
Source: Combinatorial Chemistry and High Throughput Screening - September 16, 2015 Category: Chemistry Authors: Kratasyuk VA, Esimbekova EN Tags: Comb Chem High Throughput Screen Source Type: research

Simultaneous genotyping of four single nucleotide polymorphisms associated with risk factors of hemostasis disorders.
Abstract Multiplex simultaneous genotyping technique was developed for four polymorphisms in genes coding for blood coagulation factors and homocysteine metabolism which are considered as thrombophilia related mutations: FV Leiden, FII G20210A, MTHFR C677T, and FVII G10976A. It is based on primer extension reaction with the following bioluminescent solid-phase microassay. At that, two different in bioluminescence obelin mutants were applied to simultaneous detection of two gene allelic variants. The assay is carried out in microtiter plate format and provides fast and reliable genotyping of four single nucleotide...
Source: Combinatorial Chemistry and High Throughput Screening - September 16, 2015 Category: Chemistry Authors: Bashmakova EE, Krasitskaya VV, Frank LA Tags: Comb Chem High Throughput Screen Source Type: research

Creation of artificial luciferases to expand their analytical potential.
Abstract Bioluminescent proteins have been intensively used as high sensitive reporters in all kinds of binding assays (immuno-, nucleic acid hybridization assays, etc.) and in bioimaging. But natural luciferases do not always meet the requirements set for them as the assay reporters: thermostabitity, definite bioluminescence spectral and kinetics characteristics, stability to chemical modifications, etc. Luciferases with different appropriate characteristics as well as various luciferin derivatives were obtained using mutagenesis and chemical synthesis. Thanks to rigorous efforts of many researchers bioluminescen...
Source: Combinatorial Chemistry and High Throughput Screening - September 16, 2015 Category: Chemistry Authors: Frank LA Tags: Comb Chem High Throughput Screen Source Type: research

Simultaneous multicolor luciferase reporter assays for monitoring of multiple genes expressions.
Abstract Multicolor luciferase reporter assays are powerful tools for simultaneously monitoring the expression of several genes. Dual-color luciferase reporter assays were established in 2004 and have been used in broad range of application from basic research to applications in clinical research, e.g., drug screening and alternative toxicological tests. The advantage of this method is that it can be used to simultaneously monitor sequential and complex changes in the expression of multiple genes from the single-cell level to the tissue level. In this review, I focus on the simultaneous analysis of multiple genes ...
Source: Combinatorial Chemistry and High Throughput Screening - September 16, 2015 Category: Chemistry Authors: Ohmiya Y Tags: Comb Chem High Throughput Screen Source Type: research