Prediction of Drug Induced Liver Injury using Molecular and Biological Descriptors.
Abstract In this paper we report quantitative structure-activity models linking in vivo Drug-Induced Liver Injury (DILI) of organic molecules with some parameters both measured experimentally in vitro and calculated theoretically from the molecular structure. At the first step, a small database containing information of DILI in humans was created and annotated by experimentally observed information concerning hepatotoxic effects. Thus, for each compound a binary annotation "yes/no" was applied to DILI and seven endpoints causing different liver pathologies in humans: Cholestasis (CH), Oxidative Stress (O...
Source: Combinatorial Chemistry and High Throughput Screening - March 5, 2015 Category: Chemistry Authors: Muller C, Pekthong D, Desbans C, Alexandre E, Marcou G, Horvath D, Richert L, Varnek A Tags: Comb Chem High Throughput Screen Source Type: research

Computer-aided discovery in antimicrobial research: In silico model for virtual screening of potent and safe anti-pseudomonas agents.
Abstract Resistance of bacteria to current antibiotics is an alarming health problem. In this sense, Pseudomonas represents a genus of Gram-negative pathogens which has emerged as one of the most dangerous species causing nosocomial infections. Despite the effort of the scientific community, drug resistant strains of bacteria belonging to Pseudomonas spp. prevails. Drug discovery is a very expensive process in terms of time and financial resources. For this reason, there is an urgent need of searching for more efficient antimicrobial chemotherapies. Computer-aided methodologies could rationalize several stages inv...
Source: Combinatorial Chemistry and High Throughput Screening - March 5, 2015 Category: Chemistry Authors: Speck-Planche A, Cordeiro MN Tags: Comb Chem High Throughput Screen Source Type: research

Molecular Docking to Identify Associations between Drugs and Class I Human Leukocyte Antigens for Predicting Idiosyncratic Drug Reactions.
Abstract Idiosyncratic drug reactions (IDRs) are rare, somewhat dose-independent, patient-specific and hard to predict. Human leukocyte antigens (HLAs) are the major histocompatibility complex (MHC) in humans, are highly polymorphic and are associated with specific IDRs. Therefore, it is important to identify potential drug-HLA associations so that individuals who would develop IDRs can be identified before drug exposure. We harvested the associations between drugs and class I HLAs from the literature. The results revealed that there are many drug-HLA pairs without clinical data. For better potential interactions ...
Source: Combinatorial Chemistry and High Throughput Screening - March 5, 2015 Category: Chemistry Authors: Luo H, Du T, Zhou P, Yang L, Mei H, Ng H, Zhang W, Shu M, Tong W, Shi L, Mendrick DL, Hong H Tags: Comb Chem High Throughput Screen Source Type: research

Rational Drug Design Paradigms: The Odyssey for designing better Drugs.
Abstract Due to the time and effort requirements for the development of a new drug, and the high attrition rates associated with this developmental process, there is an intense effort by academic and industrial researchers to find novel ways for more effective drug development schemes. The first step in the discovery process of a new drug is the identification of the lead compound. The modern research tendency is to avoid the synthesis of new molecules based on chemical intuition, which is time and cost consuming, and instead to apply in silico rational drug design. This approach reduces the consumables and human ...
Source: Combinatorial Chemistry and High Throughput Screening - March 5, 2015 Category: Chemistry Authors: Kellici T, Ntountaniotis D, Vrontaki E, Liapakis G, Moutevelis-Minakakis P, Kokotos G, Hadjikakou S, Tzakos AG, Afantitis A, Melagraki G, Bryant S, Langer T, Marzo VD, Mavromoustakos T Tags: Comb Chem High Throughput Screen Source Type: research

The Monte Carlo method based on eclectic data as an efficient tool for predictions of endpoints for nanomaterials - two examples of application.
Abstract The theoretical predictions of endpoints related to nanomaterials are attractive and more efficient alternatives for their experimental determinations. Such type of calculations for the "usual" substances (i.e. non nanomaterials) can be carried out with molecular graphs. However, in the case of nanomaterials, descriptors traditionally used for the quantitative structure - property / activity relationships (QSPRs/QSARs) do not provide reliable results since the molecular structure of nanomaterials, as a rule, cannot be expressed by the molecular graph. Innovative principles of computational predi...
Source: Combinatorial Chemistry and High Throughput Screening - March 5, 2015 Category: Chemistry Authors: Toropov AA, Toropova AP, Veselinović AM, Veselinović JB, Nesmerak K, Raska I, Duchowicz PR, Castro EA, Kudyshkin VO, Leszczynska D, Leszczynski J Tags: Comb Chem High Throughput Screen Source Type: research

Exploring Structural Requirements of Imaging Agents against Aβ Plaques in Alzheimer's Disease: A QSAR approach.
In this study, we have also designed some imaging agents based on the information provided by the models. Some of these designed compounds were predicted to be similar to or more active than the most active imaging agents present in the original dataset. PMID: 25747447 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - March 5, 2015 Category: Chemistry Authors: Ambure P, Roy K Tags: Comb Chem High Throughput Screen Source Type: research

LiSIs: An Online Scientific Workflow System for Virtual Screening.
We describe the overall design of the system as well as the implementation of its various components. The LiSIs platform consists of the following layers: the input layer covering the data file input; the pre-processing layer covering the descriptors calculation, and the docking preparation components; the processing layer covering the attribute filtering, compound similarity, substructure matching, docking prediction, predictive modelling and molecular clustering; post-processing layer covering the output reformatting and binary file merging components; output layer covering the storage component. The potential of LiSIs p...
Source: Combinatorial Chemistry and High Throughput Screening - March 5, 2015 Category: Chemistry Authors: Kannas CC, Kalvari I, Lambrinidis G, Neophytou CM, Savva CG, Kirmitzoglou I, Antoniou Z, Achilleos KG, Scherf D, Pitta CA, Nicolaou CA, Mikros E, Promponas VJ, Gerhauser C, Mehta RG, Constantinou AI, Pattichis CS Tags: Comb Chem High Throughput Screen Source Type: research

A Ligand-Based Virtual Screening Approach to Identify Small Molecules as hERG Channel Activators.
Abstract The hERG potassium channel is currently emerging as a potential target for the treatment of some forms of arrhythmias or to contrast an unintentional channel block caused by drugs. Despite its therapeutic relevance, so far only few compounds are described as able to enhance channel function by potentiating hERG currents. This gap is also related to the lack of hERG crystal structure which strongly limits the possibility to employ structure-based techniques in the search and design of novel activators. To overcome this limitation, in the present work, a ligand-based virtual screening was performed using as...
Source: Combinatorial Chemistry and High Throughput Screening - March 5, 2015 Category: Chemistry Authors: Giacomini E, Buonfiglio R, Masetti M, Wang Y, Tseng GN, Roberti M, Recanatini M Tags: Comb Chem High Throughput Screen Source Type: research

Determination of Antiproliferative Activities of Volatile Contents and HPLC Profiles of Dicranum scoparium (Dicranaceae, Bryophyta).
emirtas I Abstract The aim of this study was to examine the anticancer activities and phytochemical profiles of Dicranum scoparium against HeLa cell lines. The bio-guided fractionation studies of dichloromethane extract hashave high antiproliferative activities. Fractions 7, 9, 19, 20 aare rich source of unsaturated fatty acids, and- in the case of Fr-19-may improve the antiproliferative activities and alsoas well as increase the unsaturated fatty acid content. The effect of proliferative activities in hexane extract can be attributed to the saturated fatty acid composition of D. scoparium. The Fr-9 exhibited stro...
Source: Combinatorial Chemistry and High Throughput Screening - March 4, 2015 Category: Chemistry Authors: Abay G, Altun M, Koldaş S, Tüfekçi AR, Demirtas I Tags: Comb Chem High Throughput Screen Source Type: research

Ultrasonic Assisted Synthesis of Chromenes Catalyzed by Sodium Carbonate in Aqueous Media.
Abstract A simple, efficient, and environmentally benign procedure for synthesis of 2-amino-4H-chromene ring has been achieved by the three-component reaction of an aromatic aldehyde, malononitrile and diverse enolizable C-H activated compounds under ultrasound irradiation using sodium carbonate as a catalyst in aqueous media. Sodium carbonate as a natural salt, available, inexpensive catalyst combined with ultrasound method which promoted this protocol in comparison of other methods and catalysts. PMID: 25708865 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - February 23, 2015 Category: Chemistry Authors: Sabbaghan M, Sofalgar P Tags: Comb Chem High Throughput Screen Source Type: research

Editorial: peer review pitfalls.
PMID: 25692538 [PubMed - in process] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - February 20, 2015 Category: Chemistry Authors: Chaguturu R Tags: Comb Chem High Throughput Screen Source Type: research

Editorial (thematic issue: application of chemometrics and cheminformatics in antimalarial drug research).
PMID: 25692659 [PubMed - in process] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - February 20, 2015 Category: Chemistry Authors: Roy K Tags: Comb Chem High Throughput Screen Source Type: research

A Selective, Expeditious and Sustainable Entry en Route to Benzopyrazines and Bis-Benzopyrazines.
Abstract A convenient green synthesis of benzopyrazines and bis-benzopyrazines has been performed by the condensation of diversely substituted diamines and dicarbonyl compounds in water using indium powder as catalyst under controlled microwave exposure. The effects of microwave power, and temperature on this reaction are investigated in detail to identify the best condition. A wide range of diversely substituted diamines and dicarbonyl compounds produce excellent yield of the corresponding benzopyrazines and bis-benzopyrazines. A comparative study has also been made between microwave-induced procedure and convent...
Source: Combinatorial Chemistry and High Throughput Screening - January 31, 2015 Category: Chemistry Authors: Bandyopadhyay D, Mukherjee S, Banik BK Tags: Comb Chem High Throughput Screen Source Type: research

Quantitative Prediction of Class I MHC/Epitope Binding Affinity using QSAR Modeling Derived from Amino Acid Structural Information.
In this study, a comprehensive quantitative prediction method of binding affinity was established using quantitative structure-activity relationship (QSAR) modeling derived from amino acid physicochemical information. Firstly, the epitope was characterized by a set of amino acid physicochemical parameters. Secondly, the structural variables were optimized by the stepwise regression (STR). Finally, the robust quantitative models with were built by multiple linear regressions (MLR) for 31 MHC class I subtypes. The normalized regression coefficients (NRCs) of QSAR model could demonstrate the mechanism of interaction of MHC, e...
Source: Combinatorial Chemistry and High Throughput Screening - January 21, 2015 Category: Chemistry Authors: Wang Y, Zhou P, Lin Y, Shu M, Hu Y, Xia Q, Lin Z Tags: Comb Chem High Throughput Screen Source Type: research

Discovery of Anti-malarial Agents Through Application of In silico Studies.
Abstract Among the various parasitic diseases, malaria is the deadliest one. Due to the emergence of high drug resistance to the existing drug candidates there is a global need for development of new drug candidates which will be effective against resistant strains of malaria parasite. In silico molecular modeling approaches have been playing an important role in the discovery of novel lead molecules having antimalarial activity. Present review is an effort to cover all the developments related to the application of computational techniques for the design and discovery of novel antimalarial compounds since the yea...
Source: Combinatorial Chemistry and High Throughput Screening - December 29, 2014 Category: Chemistry Authors: Barmade MA, Murumkar PR, Sharma MK, Shingala KP, Giridhar RR, Yadav MR Tags: Comb Chem High Throughput Screen Source Type: research

The Current Status of Antimalarial Drug Research with Special Reference to Application of QSAR Models.
Abstract Malaria, the most virulent parasitic disease, has become a devastating global health issue in tropical and subtropical regions, especially in Africa where the temperature and rainfall are most suitable for the development of the causative vector. Due to the spread of multidrug resistance to the currently available antimalarial drugs including the "magic bullet" artemisinin, discovery and development of new antimalarial drugs is one of the utmost challenges. Different government and non-government chemical regulatory authorities have recommended the application of non-animal, alternative techniqu...
Source: Combinatorial Chemistry and High Throughput Screening - December 29, 2014 Category: Chemistry Authors: Ojha PK, Roy K Tags: Comb Chem High Throughput Screen Source Type: research

New Horizons in Antimalarial Drug Discovery in the Last Decade by Chemoinformatic Approaches.
Abstract Antimalarial drug discovery process is progressively carried out by a combination of innovation and knowledge based methods that includes computational and experimental to achieve potent leads. Among the various computational approaches, chemoinformatics has a critical role to play in the discovery of new leads or drug candidates. Chemoinformatics provides researchers tools to derive information on substructures, chemical space, similarity and diversity. It also helps to manage and store chemical data, study important molecular properties and filter libraries with regard to specified criteria in the datab...
Source: Combinatorial Chemistry and High Throughput Screening - December 29, 2014 Category: Chemistry Authors: Ambre PK, Wavhale RD, Coutinho EC Tags: Comb Chem High Throughput Screen Source Type: research

3D-QSAR studies on Plasmodium falciparam proteins: A Mini-Review.
Abstract 3D-QSAR has become a very important tool in the field of Drug Discovery, especially in important areas like malarial research. The 3D-QSAR is principally a ligand-based drug design but the bioactive conformation of the ligand can also be taken into account in constructing a 3D-QSAR model. The induction of receptor-based 3D-QSAR has been proven to give more robust statistical models. In this review, we have discussed the various 3D-QSAR works done so far which were aimed at combating malaria caused by Plasmodium falciparam. We have also discussed the various enzymes/receptors (targets) in Plasmodium falcip...
Source: Combinatorial Chemistry and High Throughput Screening - December 29, 2014 Category: Chemistry Authors: Divakar S, Hariharan S Tags: Comb Chem High Throughput Screen Source Type: research

Understanding the Structural Requirements in Diverse Scaffolds for the Inhibition of P. Falciparum Dihydroorotate Dehydrogenase (PfDHODH) using 2D-QSAR, 3D-Pharmacophore and Structure-Based Energy-Optimized Pharmacophore Models.
Abstract P. falciparum dihydroorotate dehydrogenase (PfDHODH) of the pyrimidine biosynthetic pathway offers a promising target for the development of antimalarial drugs in the scenario of widespread falciparum resistance. In this background, we have made an effort to decipher the structural requirements for the inhibition of PfDHODH using regression-based 2D-QSAR, 3D-pharmacophore modeling and energy-based pharmacophoric (e-pharmacophore) studies. The 2D-QSAR and 3D-pharmacophore models were built from a structurally diverse set of 38 dihydrothiophenone derivatives, while the e-pharmacophore models were developed ...
Source: Combinatorial Chemistry and High Throughput Screening - December 29, 2014 Category: Chemistry Authors: Aher RB, Roy K Tags: Comb Chem High Throughput Screen Source Type: research

Molecular Modelling Based Target Identification for Endo-Peroxides Class of Antimalarials.
Abstract The emerging cases of artemisinin and related drug resistance is becoming a challenge to antimalarial drug discovery and therapy. The precise mechanism of action of this class of antimalarials is still unknown which presents a bottleneck for the understanding of drug resistance as well as designing of new lead molecules of this class. To address this issue, the molecular docking and scoring studies of a homogeneous and structurally diverse dataset of artemisinin derived trioxanes have been performed on each of the two plausible targets of this class viz. heme and PfATP6. Since the crystal structure of PfA...
Source: Combinatorial Chemistry and High Throughput Screening - December 29, 2014 Category: Chemistry Authors: Gupta AK, Saxena AK Tags: Comb Chem High Throughput Screen Source Type: research

Discovery of New Potential Antimalarial Compounds Using Virtual Screening of ZINC Database.
In this study, a support vector machine (SVM) model based on fingerprint based descriptors was developed on a dataset of 239 FP-3 inhibitors to identify the most active antimalarial compounds among the active compounds provided from similarity search. The satisfactory classification performance achieved by the SVM model shows its ability to use it as a further filter to distinguish the most active compounds. The accuracy in prediction for the training, test and external validation sets were 97.39%, 94.74% and 90.6%, respectively. Furthermore, the performance of the model was examined by plotting the receiver operating char...
Source: Combinatorial Chemistry and High Throughput Screening - December 29, 2014 Category: Chemistry Authors: Ghasemi JB, Shiri F, Pirhadi S, Heidari Z Tags: Comb Chem High Throughput Screen Source Type: research

Exploring MIA-QSARs' for Antimalarial Quinolon-4(1H)-Imines.
Abstract A series of quinolon-4(1H)-imines have been recently discovered as antimalarials, targeting both the exoerythrocytic and erythrocytic stages of the parasite's development stages, which correspond to the phase of clinical symptoms. Endowed with chemical and metabolic stability, the quinolon-4(1H)-imines are thus presented as promissory dual-stage antimalarials. Three versions of multivariate image analysis applied to quantitative structure-activity relationship (MIA-QSAR) methods, namely traditional MIA-QSAR, augmented MIA-QSAR (aug-MIA-QSAR) and color-encoded aug-MIA-QSAR (aug-MIA-QSARcolor), were applied...
Source: Combinatorial Chemistry and High Throughput Screening - December 29, 2014 Category: Chemistry Authors: Duarte MH, Barigye SJ, Freitas MP Tags: Comb Chem High Throughput Screen Source Type: research

Virtual High-Throughput Screening of Carbapenem Derivatives as New Generation Carbapenemase and Penicillin Binding Protein Inhibitors: A Hunt to Save Drug of Last Resort.
Abstract The advent of carbapenem resistance by the production of β-lectamases and mutated penicillin binding proteins (PBPs) has challenged the treatment of Enterobacteriaceae. Hence there is an urgent need to establish drugs that can fit in the pipeline by overcoming those situations. The hypotheses of the work is based on two facts, i.e., i) design of inhibitors against mutated PBPs to which present drugs cannot bind efficiently to kill pathogen by inhibiting cell wall formation, ii) design of molecules that can bind with β-lectamases with high affinity, so that they can supplement available drugs pre...
Source: Combinatorial Chemistry and High Throughput Screening - December 26, 2014 Category: Chemistry Authors: Chowdhury A, Paul P, Bhattacharjee A, Talukdar AD, Choudhury MD Tags: Comb Chem High Throughput Screen Source Type: research

Analytical Characterization of Label-free Immunosensor Subsystems Based on Multi-Walled Carbon Nanotube Array-Modified Gold Interface.
Abstract In the present work, we report characterization studies of antigen(Ag)-antibody (Ab) interaction based on the multi-walled carbon nanotube array-modified gold electrode for label-free electrochemical immunosensor. -COOH functionalization of MWCNT was suggested by FTIR spectroscopy. Images from atomic force microscopy (AFM) and RAMAN spectroscopy confirmed the interaction of Ab on the gold interface based on the MWCNT array. A cyclic voltammetric study exhibited a linear response in phosphate buffered saline (PBS) solution including 1mM K3Fe (CN) 6 at pH 7.4 with PSA concentrations over a range of 2 to 40 ...
Source: Combinatorial Chemistry and High Throughput Screening - December 12, 2014 Category: Chemistry Authors: Zahmatkeshan M, Ilkhani H, Paknejad M, Adel M, Sarkar S, Saber R Tags: Comb Chem High Throughput Screen Source Type: research

Computational Insights Into the Inhibition of Influenza Viruses by Rupestonic Acid Derivatives: Pharmacophore Modeling, 3D-QSAR, CoMFA and COMSIA Studies.
Abstract The pharmacophore modeling and 3D-QSAR studies were performed on a series of amino alkyl rupestonates (Rupestonic Acid) derivatives reported for H1N1, H3N2 and influenza B virus, NA inhibition. In order to improve the efficacy of amino alkyl rupestonates derivatives a four point pharmacophore model with one acceptor and three hydrophobic regions was developed. Furthermore, the 3D-QSAR model was generated based on the pharmacophore hypothesis (AHHH) for each subtype. The hypothesis is more significant with R²=0.9204, Q²=0.917 for H1N1, R²=0.8911, Q²=0.8905 for H3N2 and R²=0.8385, Q...
Source: Combinatorial Chemistry and High Throughput Screening - December 7, 2014 Category: Chemistry Authors: Muthusamy K, Kirubakaran P, Krishnasamy G, Than RR Tags: Comb Chem High Throughput Screen Source Type: research

Discovery of MINC1, a GTPase-Activating Protein Small Molecule Inhibitor, Targeting MgcRacGAP.
Abstract The Rho family of Ras superfamily small GTPases regulates a broad range of biological processes such as migration, differentiation, cell growth and cell survival. Therefore, the availability of small molecule modulators as tool compounds could greatly enhance research on these proteins and their biological function. To this end, we designed a biochemical, high throughput screening assay with complementary follow-up assays to identify small molecule compounds inhibiting MgcRacGAP, a Rho family GTPase activating protein involved in cytokinesis and transcriptionally upregulated in many cancers. We first perf...
Source: Combinatorial Chemistry and High Throughput Screening - December 4, 2014 Category: Chemistry Authors: van Adrichem J, Fagerholm A, Turunen L, Lehto A, Saarela J, Koskinen A, Repasky GA, Wennerberg K Tags: Comb Chem High Throughput Screen Source Type: research

ZnO-Nanorods as the Catalyst for the Synthesis of 1,3-Thiazole Derivatives Via Multicomponent Reactions.
Abstract Environmentally method for the synthesis of 1,3-thiazole has been achieved by multicomponent reactions of primary amines, isothiosyanates and alkyl bromides under solvent-free conditions using nanorod ZnO structures as catalyst. These reactions weren't performed without catalyst. The catalyst showed significant reusable activity. PMID: 25469698 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - December 3, 2014 Category: Chemistry Authors: Hajinasiri R, Hossaini Z, Sheikholeslami-Farahani F Tags: Comb Chem High Throughput Screen Source Type: research

In Silico Classification and Prediction of VIP Derivatives as VPAC1/VPAC2 Receptor Agonists/Antagonists.
Abstract Vasoactive intestinal polypeptide (VIP) is an intrinsic 28-amino acid peptide, involved in a wide range of physiologic effects, and therefore considered as a promising drug candidate for the treatment of several diseases. But the clinical application of VIP has been limited for the easy in vivo digestion. Various researches aiming to prolong the VIP half-life, by modifying the VIP structure, have been reported. The first thing to be considered after structural modification is to know it is a VPAC agonist or antagonist. To analyze the structure-activity relationships of VIP derivatives and build classifier...
Source: Combinatorial Chemistry and High Throughput Screening - November 27, 2014 Category: Chemistry Authors: Li J, Wang X, Liu H, Li H Tags: Comb Chem High Throughput Screen Source Type: research

Synthesis and Antitubercular Screening of some Novel 4H-1,4-Benzothiazines and their Sulfones Under Environment Benign Solvent Free Conditions as Future Anti-Tubercular Agents.
Abstract Some novel analogs of 4H-1,4-benzothiazines were synthesized under environmentally benign solvent free conditions by one pot oxidative cyclocondensation of substituted 2-aminobenzenthiols with compounds having active methylene group and then converted in to sulfones. These compounds were examined as antitubercular agents against Mycobacterium tuberculosis H37Rv using REMA plate method. The best results have MICs from 6.4 to 8.8 µg/mL , comparable to phenothiazines. IR, NMR and mass spectral investigations are included for structural elucidation. PMID: 25426761 [PubMed - as supplied by publisher...
Source: Combinatorial Chemistry and High Throughput Screening - November 26, 2014 Category: Chemistry Authors: Guleria A, Jangid DK, Gautam N, Lakhotia R, Chowdhary A, Gautam DC Tags: Comb Chem High Throughput Screen Source Type: research

Editorial: computational toxicology: screening, chemistry, or much more?
PMID: 25403346 [PubMed - in process] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - November 22, 2014 Category: Chemistry Authors: Lushington GH Tags: Comb Chem High Throughput Screen Source Type: research

Classification Models of HCV NS3 Protease Inhibitors based on Support Vector Machine (SVM).
Abstract Inhibition of the hepatitis C virus (HCV) non-structural protein 3 (NS3) serine protease by molecule inhibitors is an attractive strategy for the treatment of hepatitis C. We built four classification models based on a dataset of 413 HCV NS3 protease inhibitors using support vector machine method. The best performing model obtains the best prediction performance for the test set with prediction accuracy, sensitivity (SE), specificity (SP) and Matthews correlation coefficient (MCC) of 90.76%, 92.21%, 88.10% and 0.799. The number of rotatable bonds (NRotBond), charge and electronegativity related properties...
Source: Combinatorial Chemistry and High Throughput Screening - November 20, 2014 Category: Chemistry Authors: Wang M, Xuan S, Yan A, Yu C Tags: Comb Chem High Throughput Screen Source Type: research

Molecular structural characteristics important in drug-HSA binding.
Abstract A non-linear quantitative structure activity relationship (QSAR) model based on 350 drug molecules was developed, as a predictive tool for drug protein binding, by correlating experimentally measured protein binding values with ten calculated molecular descriptors using a radial basis function (RBF) neural network. The developed model has a statistically significant overall correlation value (r> 0.73), a high efficiency ratio (0.986), and a good predictive squared correlation coefficient (q2) of 0.532, which is regarded as producing a robust and high quality QSAR model. The developed model may be used ...
Source: Combinatorial Chemistry and High Throughput Screening - November 14, 2014 Category: Chemistry Authors: Agatonovic-Kustrin S, Morton DW, Truong L, Razic S Tags: Comb Chem High Throughput Screen Source Type: research

The Application of Connected QSRR and QSAR Strategies to Predict the Physicochemical Interaction of Acridinone Derivatives with DNA.
Abstract Acridinone derivatives as imidazoacridinones and triazoloacridinones are the new potent antitumor agents characterized by different mechanisms of action related to their ability to interact with DNA. The analysis undertaken in this study involves searching of QSAR (Quantitative Structure-Activity Relationship) and QSRR (Quantitative Structure-Retention Relationship) models, which would allow to predict the biological activity of acridinones expressed as ability to stabilize the secondary structure of DNA (∆T), based on their structural parameters and chromatographic retention data. For this purpose, 20 ...
Source: Combinatorial Chemistry and High Throughput Screening - November 12, 2014 Category: Chemistry Authors: Paulina S, Marcin K, Agata K, Sylwia K, Emilia D, Bączek T Tags: Comb Chem High Throughput Screen Source Type: research

Green synthesis of phosphoryl-2-oxo-2H-pyran via three component reaction of trialkyl phosphites.
Abstract An effective one-pot synthesis of dialkoxyphosphoryl-2-oxo-2H-pyran derivatives by three-component reaction of alky bromides and dialkyl acetylenedicarboxylates in the presence of trialkyl phosphite is described. The reactions were performed under solvent-free conditions at 50oC and neutral conditions and provided good yields of products. PMID: 25386707 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - November 11, 2014 Category: Chemistry Authors: Hossaini Z, Sheikholeslami-Farahani F, Rostami-Charati F Tags: Comb Chem High Throughput Screen Source Type: research

Green Synthesis of Phosphoryl-2-oxo-2H-Pyran Via Three Component Reaction of Trialkyl Phosphites.
Abstract An effective one-pot synthesis of dialkoxyphosphoryl-2-oxo-2H-pyran derivatives by three-component reaction of alky bromides and dialkyl acetylenedicarboxylates in the presence of trialkyl phosphite is described. The reactions were performed under solvent-free conditions at 50oC and neutral conditions and provided good yields of products. PMID: 25373506 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - November 6, 2014 Category: Chemistry Authors: Hossaini Z, Sheikholeslami-Farahani F, Rostami-Charati F Tags: Comb Chem High Throughput Screen Source Type: research

In Vitro High-Throughput Phage Display Selection of Ovarian Cancer Avid Phage Clones for Near-Infrared Optical Imaging.
Abstract Ovarian cancer is among the leading causes of cancer deaths in women, and is the most fatal gynecological malignancy. Poor outcomes of the disease are a direct result of inadequate detection and diagnostic methods, which may be overcome by development of novel efficacious screening modalities. However, the advancement of such technologies is often time-consuming and costly. To overcome this hurdle, our laboratory has established a time and cost effective method of selecting and identifying ovarian carcinoma avid bacteriophage (phage) clones using high-throughput phage display technology. These phage clone...
Source: Combinatorial Chemistry and High Throughput Screening - October 31, 2014 Category: Chemistry Authors: Soendergaard M, Newton-Northup JR, Deutscher SL Tags: Comb Chem High Throughput Screen Source Type: research

Rapid Screening of Different types of Antitumor Compound Groups from Traditional Chinese Medicine by Hollow Fiber Cell Fishing with High Performance Liquid Chromatography.
In this study, three cells (MCF-7, SGC7901, and MADB-106) were seeded on the inner wall of the hollow fiber employed to screen bioactive components from TCM water decoction. The variables influencing HFCF-HPLC, such as cell seeding time, screening stirring rate and time, and active compound concentration, were investigated and optimized. The surface property of the hollow fiber seeded with cells, the cell survival rate under different conditions, the nonspecific binding between active centers in the fiber and the target compounds, and the repeatability and recovery of HFCF-HPLC were analyzed and validated. Certain structur...
Source: Combinatorial Chemistry and High Throughput Screening - October 30, 2014 Category: Chemistry Authors: Zhang LS, Chen X, Hu S, Sheng X, Bai XH Tags: Comb Chem High Throughput Screen Source Type: research

Design Novel Inhibitors for Treating Cancer by Targeting Cdc25B Catalytic Domain with de Novo Design.
Abstract The cell division cycle 25 (Cdc25) families of proteins are highly conserved dual specificity phosphatases that regulate cyclin-dependent kinases and represent a group of attractive drug targets for anticancer therapies. To develop novel Cdc25B inhibitors, the ZINC database was screened for finding the optimal fragments with de novel design approaches. As a result, top 11 compounds having higher binding affinities in flexible docking were obtained, which were derived from five novel scaffolds consisting of two isolated scaffolds located in the two binding domains (catalytic pocket and swimming pool) and t...
Source: Combinatorial Chemistry and High Throughput Screening - October 29, 2014 Category: Chemistry Authors: Wu JW, Zhang H, Duan YQ, Dong WL, Cheng XC, Wang SQ, Wang RL Tags: Comb Chem High Throughput Screen Source Type: research

Ligand-Based Pharmacophore Modeling, Atom-Based 3D-QSAR and Molecular Docking Studies on Substituted Thiazoles and Thiophenes as Polo-Like Kinase 1 (Plk1) Inhibitors.
Abstract Polo-like kinase 1 (Plk1) is a decisive enzyme with its multifunctional activity in cell cycle progression especially mitosis. The over expression of Plk1 in broad spectrum of cancer types turn into a promising therapeutic target against cancer. In the present study, several ligand based pharmacophore models and atom based 3D-QSAR models have been generated using a series of 49 thiazole and thiophene derivatives with well prescribed Plk1 inhibitory activity. From the generated models, the AADRR hypothesis associated with an atom based 3D-QSAR model provided a satisfactory statistical significance containi...
Source: Combinatorial Chemistry and High Throughput Screening - October 24, 2014 Category: Chemistry Authors: Chekkara R, Gorla VR, Susithra E, Tenkayala SR Tags: Comb Chem High Throughput Screen Source Type: research

In Silico Modelling of Pesticide Aquatic Toxicity.
Abstract Human activities have introduced tens of thousands of chemicals into water systems around the world which has significantly impacted water quality and aquatic ecosystems. The aim of this study was to develop an in silico QSAR model, capable of predicting the aquatic toxicity of pesticides in terms of a lethal dose (LD50) for fish without requiring the use of in vivo testing. A large data set of 230 diverse pesticides, including fungicides, herbicides and insecticides, with experimentally measured LD50 values was used to develop a predictive QSAR model. Each pesticide molecule was described using 62 calcul...
Source: Combinatorial Chemistry and High Throughput Screening - October 21, 2014 Category: Chemistry Authors: Agatonovic-Kustrin S, Morton DW, Razic S Tags: Comb Chem High Throughput Screen Source Type: research

In Silico Screening of Drugs to Find Potential Gamma-Secretase Inhibitors Using Pharmacophore Modeling, QSAR and Molecular Docking Studies.
Abstract Modulation of gamma-secretase cleavage of Amyloid Precursor Protein (APP) to control the level of Amyloid-beta (A-beta) peptide is one of the strategies to develop therapy for Alzheimer's disease. Presenilin is a subunit and the catalytic core of gamma-secretase. It has Asp 257 and Asp 385 residues, which are essential for catalytic activity and thus serve as the region of interest for screening of potential gamma-secretase inhibitors. In the present study, in silico screening of drug molecules has been performed in an attempt to identify effective inhibitors of presenilin. Ligand-based pharmacophore mode...
Source: Combinatorial Chemistry and High Throughput Screening - October 19, 2014 Category: Chemistry Authors: Arun EV, Krishnan K, Maurya A, Sarkar N Tags: Comb Chem High Throughput Screen Source Type: research

Establishment Of A Novel Whole Animal HTS Technology Platform For Melioidosis Drug Discovery.
Abstract Melioidosis is a serious emerging endemic infectious disease caused by Burkholderia pseudomallei, a gram-negative pathogen. Septicemic melioidosis has a mortality rate of 50% even with treatment. Like other gramnegative bacteria, B. pseudomallei is resistant to a number of antibiotics and multi-drug resistant B. pseudomallei is beginning to be encountered in hospitals. There is a clear medical need to develop new treatment options to manage this disease. We used Burkholderia thailandensis (a BSL-2 class organism) to infect Caenorhabditis elegans and set up a surrogate whole animal infection model of melio...
Source: Combinatorial Chemistry and High Throughput Screening - October 19, 2014 Category: Chemistry Authors: Lakshmanan U, Yap A, Fulwood J, Yichun L, Hoon SS, Lim J, Ting A, Sim XH, Kreisberg J, Tan P, Tan G, Flotow H Tags: Comb Chem High Throughput Screen Source Type: research

A Simple, Efficient and Environmentally Benign Synthetic Protocol for the Synthesis of Spirooxindoles using Choline Chloride-Oxalic Acid Eutectic Mixture as Catalyst/Solvent System.
Abstract An efficient and environmentally benign domino protocol has been presented for the synthesis of structurally diverse spirooxindoles spiroannulated with pyranopyridopyrimidines, indenopyridopyrimidines, and chromenopyridopyrimidines involving three-component reaction of aminouracils, isatins and cyclic carbonyl compounds in deep eutectic solvent (choline chloride-oxalic acid: 1:1) which acts as efficient catalyst and environmentally benign reaction medium. The present protocol offers several advantages such as operational simplicity with easy workup, shorter reaction times excellent yields with superior at...
Source: Combinatorial Chemistry and High Throughput Screening - October 16, 2014 Category: Chemistry Authors: Khandelwal S, Rajawat A, Tailor YK, Kumar M Tags: Comb Chem High Throughput Screen Source Type: research

Editorial: mining for pharmacophores in phenotypic screens.
Abstract Let's consider the growing popularity of phenotypic screens within the drug development community. Biochemical assays once dominated the field of high throughput chemical screening, but phenotypic experiments are more adept at modeling real physiological behavior, and can simultaneously mimic drug delivery factors including cell membrane permeability, intracellular localization, and aspects of transport and metabolism. Efficiency and cost of phenotypic screens have improved substantially over the years. For all of these reasons, the technology is well suited to fostering lead optimization. The technology ...
Source: Combinatorial Chemistry and High Throughput Screening - October 2, 2014 Category: Chemistry Authors: Lushington GH Tags: Comb Chem High Throughput Screen Source Type: research

Molecular Dynamic Simulation and Spectroscopic Investigation of Some Cytotoxic Palladium(II) Complexes Interaction with Human Serum Albumin.
Abstract Studies on the interactions between metallodrugs and human serum albumin (HSA), as carrier for drugs and biological molecules, are extremely important to design and discover new drugs. The interaction of three novel synthesized complexes of [Pd(phen)(R-gly)]NO3, where R-gly is methyl-, propyl-, and amyl-glycine and phen is 1,10-phenanthroline, with HSA were investigated using spectroscopic studies in combination with a molecular dynamic simulation. These water soluble complexes can denature HSA at ~50 µM. According to the results obtained for the isothermal titration at 27 and 37 °C, it was foun...
Source: Combinatorial Chemistry and High Throughput Screening - September 26, 2014 Category: Chemistry Authors: Moghadam ME, Saidifar M, Rostami-Charati F, Ajloo D, Ghadamgahi M, Farhangian H, Abolhosseini SA Tags: Comb Chem High Throughput Screen Source Type: research

Development of a Simple and Efficient Solution-Phase Parallel Synthesis of Flexible Non-Steroidal Estradiol Mimics.
Abstract An efficient parallel synthesis was designed to provide libraries of estradiol mimics that can potentially interact with different biological targets associated with estradiol-related diseases. Two libraries comprised of 75 members each were synthesized around a non-steroidal core by adding three levels of molecular diversity. Hydroxybenzaldehydes (1st level of diversity), protected as a methoxymethyl ether, first reacted with primary amines (2nd level of diversity) under reductive amination conditions. The resulting secondary amines next reacted with 4-bromo-1,2-epoxybutane to provide epoxide derivatives...
Source: Combinatorial Chemistry and High Throughput Screening - September 15, 2014 Category: Chemistry Authors: Djigoue GB, Maltais R, Poirier D Tags: Comb Chem High Throughput Screen Source Type: research

First Report on Two-Fold Classification of Plasmodium Falciparum Carbonic Anhydrase Inhibitors using QSAR Modeling Approaches.
Abstract Quantitative structure-activity relationship (QSAR)-based classification approach is one of the important chemometric tools in drug discovery process for categorizing the target protein inhibitors into more active and less active classes. In this background, we have presented here a novel approach of two-fold QSAR-based classification modeling for the Plasmodium falciparum carbonic anhydrase (PfCA) inhibitors using 2D-QSAR and linear discriminant analysis (LDA) methods. The logic of applying this concept is to ensure more accurate classification of compounds and to draw some concrete conclusion about stru...
Source: Combinatorial Chemistry and High Throughput Screening - August 28, 2014 Category: Chemistry Authors: Aher RB, Roy K Tags: Comb Chem High Throughput Screen Source Type: research

In Vitro Selection of a Single-Stranded DNA Molecular Recognition Element for the Pesticide Malathion.
Abstract Many large-scale applications of the organophosphate pesticide malathion have led to widespread environmental contamination. Concentrations are found in the environment well above those which are harmful to humans and environmental organisms. No current method of detection for this pesticide is rapid, cost-effective, and specific for malathion. Therefore, we utilized a stringent Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process to identify a Molecular Recognition Element (MRE) for malathion. This MRE was identified from a large ssDNA library and has an equilibrium dissociation cons...
Source: Combinatorial Chemistry and High Throughput Screening - August 27, 2014 Category: Chemistry Authors: Williams RM, Maher E, Sooter LJ Tags: Comb Chem High Throughput Screen Source Type: research

Diastereoselective Synthesis of N-(p-tosylsulfonyl)-2-Phenylaziridine Over a Novel Magnetically Recyclable Cu(II) Catalyst Accompanied with the N-Inversion Assessment at DFT.
Abstract An experimental and theoretical study is carried out on diastereoselective aziridation of styrene over a magnetically recyclable copper(II) catalyst: Cu(acac)2/NH2-T/SiO2@Fe3O4NPs. The turnover number (TON) of our heterogeneous catalyst appears considerably higher than that reported for the homogeneous Cu(acac)2. Successive applications of solid Cu(acac)2/NH2-T/SiO2@Fe3O4NPs has a slight effect on its catalytic activity. Between anticipated cis and trans diastereomeric products, formation of only one is suggested by NMR. Even though, the trans-invertomer appears thermodynamically more stable at B3LYP/AUG-...
Source: Combinatorial Chemistry and High Throughput Screening - August 18, 2014 Category: Chemistry Authors: Ghavami M, Koohi M, Ahmadi A, Zandi H, Kassaee MZ Tags: Comb Chem High Throughput Screen Source Type: research

QSAR of Antitrypanosomal Activities of Polyphenols and their Analogues using Multiple Linear Regression and Artificial Neural Networks.
Abstract In order to find quantitative-structure relationship for the antitrypanosomal activities (against Trypanosma brucei rhodesiense) of polyphenols that belong to the different structural groups, the multiple linear regression (MLR) and artificial neural networks (ANN) were employed. Analysis was performed on the two different size of training set (59 % and 78 % molecules in the training set), and the better MLR and ANN models was obtained for data set with the smaller training set. The best MLR model obtained with the five descriptors (R3m+, GAP, DISPv, HATS2m, JGI2) was able to account only 74 % of the vari...
Source: Combinatorial Chemistry and High Throughput Screening - August 4, 2014 Category: Chemistry Authors: Rastija V, Masand VH Tags: Comb Chem High Throughput Screen Source Type: research