Cluster based SVR-QSAR modelling for HTS records: An implementation for anticancer leads against human breast cancer.
Abstract Bioassay record of High Throughput Screening (HTS) contains compounds with high diversity. This high diversity in molecules causes an intense non-linearity into the molecular descriptors set. So to build a QSAR model covering the diversity in molecular structure is a tedious task. In the present work, a method has been proposed to extract information about pharmacophores covering a larger area in the HTS record and development of Support Vector Regression (SVR) QSAR model considering extracted pharmacophores specified to the cell line or target. A probabilistic approach has also been proposed to evaluate ...
Source: Combinatorial Chemistry and High Throughput Screening - March 14, 2013 Category: Chemistry Authors: Prakash O, Khan F Tags: Comb Chem High Throughput Screen Source Type: research

N-Lipidated Oligopeptides Immobilized on Cellulose As New Type of Organocatalysts.
Abstract A library of supramolecular structures formed by self-organization of N-lipidated tripeptides, dipeptides and N-acylated amino acids attached to cellulose according to the TASP concept via aminophenylamino-1,3,5-triazine was synthesized and the catalytic activity of the structures was studied. Intensive catalytic activity in solvolysis of sterically hindered ZAib-Aib-ONp under ambient conditions was observed for structures bearing the catalytic triad as well as for structures with the peptide fragment shortened to a dipeptide or even a single Ser, Glu or His residue, but not for structures bearing alanine...
Source: Combinatorial Chemistry and High Throughput Screening - March 14, 2013 Category: Chemistry Authors: Fraczyk J, Kolesinska B, Kaminski ZJ Tags: Comb Chem High Throughput Screen Source Type: research

Immobilized OBOC combinatorial bead array to facilitate multiplicative screening.
Abstract One-bead-one-compound (OBOC) combinatorial library screening has been broadly utilized for the last two decades to identify small molecules, peptides or peptidomimetics targeting variable screening probes such as cell surface receptors, bacteria, protein kinases, phosphatases, proteases etc. In previous screening methods, library beads were suspended in solution and screened against one single probe. Only the positive beads were tracked and isolated for additional screens and finally selected for chemical decoding. During this process, the remaining negative beads were not tracked and discarded. Here we r...
Source: Combinatorial Chemistry and High Throughput Screening - March 13, 2013 Category: Chemistry Authors: Xiao W, Bononi FC, Townsend J, Li Y, Liu R, Lam KS Tags: Comb Chem High Throughput Screen Source Type: research

A novel multi-target drug screening strategy directed against key proteins of dapk family.
Abstract Screening and identifying multi-target ligands becomes a daunting task when there are very few matching pharmacophoric features among the proteins. Herein, we describe a novel screening strategy to identify multi-target ligands for proteins having varying pharmacophoric features with their ligands. This strategy was adopted to identify multi-target ligands for death-associated protein kinase (DAPk) family. The role of the kinase activity of DAPk in eukaryotic cell apoptosis and the ability of bioavailable DAPk inhibitors to rescue neuronal death after brain injury have made it a drug-discovery target for ...
Source: Combinatorial Chemistry and High Throughput Screening - March 8, 2013 Category: Chemistry Authors: Nair SB, Fayaz SM, Rajanikant GK Tags: Comb Chem High Throughput Screen Source Type: research

Efficacy and Activity Prediction by Molecular Topology of New Drugs Against the Tetranychus Urticae Plague.
te;n R, Amigó JM Abstract Tetranychus urticae Koch is an important pest affecting citrus, for which biological control has not yet been achieved; therefore, acaricides are commonly used instead. The goal of the work reported in this paper was to measure the efficacy of different new compounds - uracil derivates - on this mite and conduct a quantitative structure-activity relationship (QSAR) study based on the results obtained, in order to set up a model capable of predicting the acaricidal activity of further new compounds. Some of the tested new products proved highly effective against T. urticae. Besides,...
Source: Combinatorial Chemistry and High Throughput Screening - March 7, 2013 Category: Chemistry Authors: Mérida S, Fustero S, Villar VM, Gálvez M, Román R, Amigó JM Tags: Comb Chem High Throughput Screen Source Type: research

A Study on Factors Affecting the Reproducibility of a Chemical Tongue Analysis Responding to Amino Acids.
Abstract Four fluorescent tricyclic basic dyes with two hollow organic capsules namely cucurbit[n]urils (CB[n]), n = 7 and 8, compose the chemical tongue that is examined for α-amino acids recognition. This array is able to identify and discriminate 18 α-amino acids up to 10-4 M without the need of enzyme activation. The paper shows the importance of the classification technique employed in order to reach the highest recognition rate at this concentration. PMID: 23477497 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - March 7, 2013 Category: Chemistry Authors: Baumes LA, Ranilla J Tags: Comb Chem High Throughput Screen Source Type: research

A Novel High-Throughput 1536-well Notch1 γ-Secretase AlphaLISA Assay.
A Novel High-Throughput 1536-well Notch1 γ-Secretase AlphaLISA Assay. Comb Chem High Throughput Screen. 2013 Feb 27; Authors: Chau DM, Shum D, Radu C, Bhinder B, Gin D, Gilchrist ML, Djaballah H, Li YM Abstract The Notch pathway plays a crucial role in cell fate decisions through controlling various cellular processes. Overactive Notch signal contributes to cancer development from leukemias to solid tumor. γ-Secretase is an intramembrane protease responsible for the final proteolytic step of Notch that releases the membrane-tethered Notch fragment for signaling. Therefore, γ-Secretase is ...
Source: Combinatorial Chemistry and High Throughput Screening - February 27, 2013 Category: Chemistry Authors: Chau DM, Shum D, Radu C, Bhinder B, Gin D, Gilchrist ML, Djaballah H, Li YM Tags: Comb Chem High Throughput Screen Source Type: research

Monoclonal Antibody-Based Fluorescence Polarization Immunoassay for High-Throughput Screening of Furaltadone and Its Metabolite AMOZ in Animal Feeds and Tissues.
Abstract A simple and fast homogeneous fluorescent polarization immunoassay (FPIA) was developed for the determination of furaltadone and its metabolite 3-amino-5-methylmorpholino-2-oxazolidinone (AMOZ). Monoclonal antibody with high cross-reactivity to furaltadone and the nitrophenyl derivative of AMOZ (NPAMOZ) were produced against a novel immunogen and the effects of several synthesized tracers on FPIA sensitivity studied. The proposed FPIA, using an optimum antibody and tracer pair, had an IC50 of 4.3 μg L-1 and limit of detection at 0.6 μg L-1 for furaltadone, and 2.7 μg L-1 and 0.3 μg L-1 for NPA...
Source: Combinatorial Chemistry and High Throughput Screening - February 25, 2013 Category: Chemistry Authors: Xu ZL, Zhang SW, Sun YM, Shen YD, Lei HT, Jiang YM, Eremin SA, Yang JY, Wang H Tags: Comb Chem High Throughput Screen Source Type: research

Combinatorial Synthesis of Pyrazoloquinoline and Pyrazolo[3,4-a]acridine Derivatives with High Regioselectivity.
Abstract Aldehyde and 1H-indazol-6-amine reacted with 1,3-dicarbonyl compounds in EtOH under catalyst-free conditions, giving corresponding pyrazolo[3,4-a]acridine, cyclopenta [b]pyrazolo[3,4-f]quinoline, indeno[1,2-b]pyrazolo[3,4-f]quinoline and benzo[h]pyrazolo[3,4-a] acridine derivatives in high yields and regioselectivity, respectively, The dicarbonyl compounds include 5,5-dimethyl cyclohexane-1,3-dione, cyclopentane-1,3-dione, 2H-indene-1,3-dione and 2-hydroxy naphthalene-1,4-dione. PMID: 23410044 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - February 11, 2013 Category: Chemistry Authors: Chen DS, Zhou YJ, Li TJ, Yao CS, Wang XS Tags: Comb Chem High Throughput Screen Source Type: research

Advanced Assessment of the Endogenous Hormone Level as a Potential Biomarker of the Urogenital Tract Cancer.
Abstract The evaluation of the relationships between the hormones involved in the urogenital tract cancer, including bladder, kidney, prostate, and testis, could prove important from diagnostic point of view. The determination of the steroid hormone profiles may likely provide a biomarker for discrimination of hormone-related diseases, as well as for differentiation of healthy volunteers from patients with cancer. The aim of the study was to demonstrate the changes in the steroid hormone profile (comprising corticosteroids, androgens and progesterone) in the urine of patients with the urogenital tract cancer versu...
Source: Combinatorial Chemistry and High Throughput Screening - February 6, 2013 Category: Chemistry Authors: Konieczna L, Belka M, Bączek T, Ruszkowski M, Struck W, Markuszewski M, Kaliszan R, Markuszewski M Tags: Comb Chem High Throughput Screen Source Type: research

Development of method for three-point data estimation and SVR-QSAR model to screen anti cancer leads.
Abstract Present work deals with generation of virtual samples as mathematical modelling of empirical data on the basis of empirical data. The generated samples were used for development of QSAR model. The method deals with extrapolation of sample vector in such a manner that there is conservation of the empirical data distribution. The data distribution has been judged with statistical parameters. The method was implemented with anticancer activity of Gossypol acetic acid against BCL2 target for colorectal cancer. Considering the virtual samples only for model development, model training showed a regression coeff...
Source: Combinatorial Chemistry and High Throughput Screening - February 6, 2013 Category: Chemistry Authors: Prakash O, Khan F Tags: Comb Chem High Throughput Screen Source Type: research

An efficient one-pot organocatalyzed synthesis of spiro[chroman-3,6'-furo[2,3-d] pyrimidine]-tetraones.
Abstract An efficient synthesis of new spiro[chroman-3,6'-furo[2,3-d]pyrimidine]-tetraones by an organocatalyzed three-component condensation reaction of aldehydes, barbituric acids and 3-bromo-4-hydroxy-2H-chromen-2-one in refluxing acetic acid in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is reported. We are hopeful that the products will lead to a wider range pharmacological and physiological activity. PMID: 23363063 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - January 28, 2013 Category: Chemistry Authors: Ahadi S, Bazgir A Tags: Comb Chem High Throughput Screen Source Type: research

Imidazoline-1 Receptor Ligands as apoptotic agents: Pharmacophore Modeling and Virtual Docking study.
In this study we examined apoptotic activity of rilmenidine (potent I1-IR agonist), moxonidine (moderate I1-IR agonist), and efaroxan (I1-IR partial agonist) on cancer cell line (K562) expressing Nischarin. The Nischarine domains mapping was performed by use of the Informational Spectrum Method. (ISM). The 3D-Quantitative Structure-Activity Relationship (3D-QSAR) and virtual docking studies of 29 I1-IR ligands (agonists, partial agonists, and antagonists) were carried out on I1-IR receptors binding affinities. The 3D-QSAR study defined 3D-pharmacophore models for I1-IR agonistic and I1-IR antagonistic activity and created ...
Source: Combinatorial Chemistry and High Throughput Screening - January 21, 2013 Category: Chemistry Authors: Nikolic K, Veljkovic N, Gemovic B, Srdic-Rajic T, Agbaba D Tags: Comb Chem High Throughput Screen Source Type: research

Larvicidal activity and click synthesis of 2-alkoxyl-2-(1,2,3-triazole-1-yl)acetamide library.
Abstract Heterogeneous copper-in-charcoal-catalyzed click synthesis in 96-well polypropylene filter plates is an efficient method for the rapid generation of  sufficient pure 2-alkoxyl-2-(1,2,3-triazole-1-yl) acetamide derivatives library by simple filtration, which directly assay the products for larvicidal activity against mosquitoes. In this procedure, copper nanoparticles on charcoal were arrayed into each well on a 96-well plate, reagents were delivered using a pipette gun, and a constant temperature shaker bath was used to complete the click reaction in 24-72 hours under temperature-controlled condition...
Source: Combinatorial Chemistry and High Throughput Screening - January 18, 2013 Category: Chemistry Authors: Su NN, Xiong LX, Yu SJ, Zhang X, Cui C, Li ZM, Zhao WG Tags: Comb Chem High Throughput Screen Source Type: research

Kf/Clinoptilolite: An Efficient Promoter For The Synthesis Of Thioethers.
Abstract Potassium fluoride impregnated on natural zeolite as a new solid base system effectively catalyzes the coupling of thiophenols with electron-deficient fluoro-, chloro- and bromo-arenes in DMSO. This versatile and efficient solid base has been demonstrated to afford the corresponding desired products in good to excellent yields. This procedure provides a convenient, efficient and practical method for the preparation of diaryl thioethers. PMID: 23360209 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - January 18, 2013 Category: Chemistry Authors: Salmanpour S, Khalilzadeh MA, Hosseini A Tags: Comb Chem High Throughput Screen Source Type: research

Nitrogen Containing Privileged Structures and their Solid Phase Combinatorial.
Abstract The existence of preferred molecular scaffolds that possess inherent biological activity, called privileged structures, is now well recognized. Such privileged structures not only provide enhanced drug-like properties but also give new hits for developing leads. The synthesis of combinatorial libraries, especially with the insertion of privileged substructures into heterocyclic moieties containing nitrogen, provides for a greater probability of the discovery of novel lead compounds using chemical transformation. The review focuses on the progress in the solid-phase synthetic strategies of nitrogen contain...
Source: Combinatorial Chemistry and High Throughput Screening - January 16, 2013 Category: Chemistry Authors: Verma A, Yadav MR, Giridhar R, Prajapati N, Tripathi AC, Saraf SK Tags: Comb Chem High Throughput Screen Source Type: research

A Theoretical study of Substitution effect on an electrocyclization reaction.
Abstract A theoretical study of substitution effect on an electrocyclization reaction was performed using DFT method at B3LYP level of theory with 6-311G** basis sets. Equilibrium molecular geometries and harmonic vibrational frequencies of the reactant, transition state (TS), and product were calculated. The considered rate constants and activation thermodynamic parameters were calculated. The results indicated the reaction is low dependent to the temperature. These calculations showed that the reaction proceeds through an asynchronous non concerted mechanism and functional group has a major effect on the reactio...
Source: Combinatorial Chemistry and High Throughput Screening - January 16, 2013 Category: Chemistry Authors: Zardoost MR, Siadati SA Tags: Comb Chem High Throughput Screen Source Type: research

Probing a chemical space for fragmental topology-activity landscapes (FRAGTAL): Application for diketo acid and catechol HIV integrase inhibitor offspring fragments.
Abstract Fragmental topology-activity landscapes (FRAGTAL), a new concept for encoding molecular descriptors for fragonomics into the framework of the molecular database records is presented in this paper. Thus, a structural repository containing biological activity data was searched in a substructure mode by a series of molecular fragments constructed in an incremental or decremental manner. The resulted series of database hits annotated with their activities construct FRAGTAL descriptors encoding a frequency of the certain fragments among active compounds and/or their activities. Actually, this method might be i...
Source: Combinatorial Chemistry and High Throughput Screening - January 16, 2013 Category: Chemistry Authors: Bak A, Magdziarz T, Kurczyk A, Serafin K, Polanski J Tags: Comb Chem High Throughput Screen Source Type: research

3D QSAR and Docking Study of Gliptin Derivatives as DPP-IV Inhibitors.
Abstract The article describes the development of a robust pharmacophore model and the investigation of structure activity relationship analysis of 46 xanthine derivatives reported for DPP-IV inhibition using PHASE module of Schrodinger software. The present works also encompass molecular interaction of 46 xanthine ligand through maestro 8.5 software. The QSAR study comprises AHHR.7 pharmacophore hypothesis, which elaborates the three points, e.g. one hydrogen bond acceptor (A), two Hydrophobic (H) and one aromatic rings (R). The discrete geometries as pharmacophoric feature was developed and the generated pharmac...
Source: Combinatorial Chemistry and High Throughput Screening - January 9, 2013 Category: Chemistry Authors: Agrawal R, Jain P, Dikshit SN, Bahare RS Tags: Comb Chem High Throughput Screen Source Type: research

Combinatorial Synthesis of a Series of Alkyl/Alkenylacyloxy Derivatives at the C-28 Position of Toosendanin as Insecticidal Agents.
Abstract In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, we have synthesized eighteen alkyl/alkenylacyloxy derivatives at the C-28 position adopting exo-configuration of toosendanin (3a-r) by the reaction of toosendanin with fatty acids in the presence of N,N'-diisopropylcarbodiimide and 4-dimethylaminopyridine. Their activity was preliminarily evaluated against the pre-third-instar larvae of Mythimna separata Walker in vivo. Especially compounds 3e and 3o displayed the more promising insecticidal activity than their natural precursor, toosendanin...
Source: Combinatorial Chemistry and High Throughput Screening - January 9, 2013 Category: Chemistry Authors: Zhang J, Qu H, Yu X, Zhi X, Chen H, Xu H Tags: Comb Chem High Throughput Screen Source Type: research

The Effect of Leverage and/or Influential on Structure-Activity Relationships.
i L Abstract In the spirit of reporting valid and reliable Quantitative Structure-Activity Relationship (QSAR) models, the aim of our research was to assess how the leverage (analysis with Hat matrix, hi) and the influential (analysis with Cook's distance, Di) of QSAR models may reflect the models reliability and their characteristics. The datasets included in this research were collected from previously published papers. Seven datasets which accomplished the imposed inclusion criteria were analyzed. Three models were obtained for each dataset (full-model, hi-model and Di-model) and several statistical validation ...
Source: Combinatorial Chemistry and High Throughput Screening - January 9, 2013 Category: Chemistry Authors: Bolboacă SD, Jäntschi L Tags: Comb Chem High Throughput Screen Source Type: research

Electrochemistry and Antioxidants.
PMID: 23305108 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - January 2, 2013 Category: Chemistry Authors: Garrido J Tags: Comb Chem High Throughput Screen Source Type: research

EDITORIAL by Rathnam Chaguturu.
PMID: 23276119 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - December 26, 2012 Category: Chemistry Authors: Chaguturu R Tags: Comb Chem High Throughput Screen Source Type: research

Rapid characterization of a novel taspine derivative-HMQ1611 binding to EGFR by a cell membrane chromatography method.
Abstract A new high-expression endothelial growth factor receptor (EGFR) cell membrane chromatography (CMC) method was applied to recognize the ligands acting on EGFR specifically, and investigate the affinity of gefitinib/HMQ1611 to EGFR. In the self and direct competitive assay, gefitinib/HMQ1611 was used as a competitor in the mobile phase to evaluate the effect of the competitor's concentrations on the retention of the ligands, respectively, and the competition between gefitinib and HMQ1611 binding to EGFR was also been examined. The retention behavior indicated that gefitinib had one type of binding sites on ...
Source: Combinatorial Chemistry and High Throughput Screening - December 18, 2012 Category: Chemistry Authors: Du H, Lv N, Wang S, He L Tags: Comb Chem High Throughput Screen Source Type: research