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In Silico Pharmacology

Umar Muzaffer, V I Paul, N Rajendra Prasad
Abstract: The signaling molecules TNF-α, AP-1, and NF-κB act to integrate multiple stress signals into a series of diverse antiproliferative responses. Disruption of these processes can promote tumor progression and chemoresistance. Naturally occurring plant derived compounds are considered as attractive candidates for cancer treatment and prevention. Phytoconstituents can control and modify various biological activities by interacting with molecules involved in concerned signaling pathways...
2017: In Silico Pharmacology
Giuseppe Deganutti, Andrei Zhukov, Francesca Deflorian, Stephanie Federico, Giampiero Spalluto, Robert M Cooke, Stefano Moro, Jonathan S Mason, Andrea Bortolato
Ligand-protein binding kinetic rates are growing in importance as parameters to consider in drug discovery and lead optimization. In this study we analysed using surface plasmon resonance (SPR) the transition state (TS) properties of a set of six adenosine A2A receptor inhibitors, belonging to both the xanthine and the triazolo-triazine scaffolds. SPR highlighted interesting differences among the ligands in the enthalpic and entropic components of the TS energy barriers for the binding and unbinding events...
2017: In Silico Pharmacology
Shivananda Kandagalla, B S Sharath, Basavapattana Rudresh Bharath, Umme Hani, Hanumanthappa Manjunatha
During metastasis, cancer cells transcend from primary site to normal cells area upon attaining epithelial to mesenchymal transition (EMT) causing malignant cancer disease. Increased expression of TGF-β and its receptor ALK5 is an important hallmark of malignant cancer. In the present study, efficacy of curcumin and its analogues as inhibitors of ALK5 (TGFβR-I) receptor was evaluated using in silico approaches. A total of 142 curcumin analogues and curcumin were retrieved from peer reviewed literature and constructed a combinatorial library...
2017: In Silico Pharmacology
Nnabuk Okon Eddy, Nsikak Bassey Essien
Molecular descriptors (including quantum chemical, topological and physicochemical descriptors) were calculated for five m-tolyl derivatives insecticides [namely, carbosulfan (CBS), carbofuran (CBF), isoprocab (IFP), methiocarb (MTC) and isocarbophos (ICP)]. Calculated quantum chemical parameters included the total energy, the electronic energy, the binding energy, the core-core repulsion energy, the heat of formation, the dipole moment and the frontier molecular orbital energies. All the calculated quantum chemical parameters (except dipole moment) exhibited strong correlation with the experimental LD50 values of the studied insecticides (at various Hamiltonians)...
2017: In Silico Pharmacology
M C Sharma, S Jain, R Sharma
To explore the relationship between the structures of substituted pyrrolidine derivatives and their inhibition of dipeptidyl peptidase IV inhibitors. The QSAR, including CoMFA, CoMSIA and HQSAR, were applied to identify the key structures impacting their inhibitory potencies. The CoMFA, CoMSIA and HQSAR with cross-validated correlation coefficient (q2 ) value of 0.727, 0.870 and 0.939 and r2 value of 0.973, 0.981 and 0.949. Based on the structure-activity relationship revealed by the present study, we have designed a set of novel dipeptidyl peptidase IV inhibitors that showed excellent potencies in the developed models...
2017: In Silico Pharmacology
Syed Ghazanfar Ali, Mohammad Azam Ansari, Qazi Mohd Sajid Jamal, Haris M Khan, Mohammad Jalal, Hilal Ahmad, Abbas Ali Mahdi
Pseudomonas aeruginosa an opportunistic pathogen regulates its virulence through Quorum sensing (QS) mechanism comprising of Las and Rhl system. Targeting of QS mechanism could be an ideal strategy to combat infection caused by P . aeruginosa . Silver nanoparticles (AgNPs) have been broadly applied as antimicrobial agents against a number of pathogenic bacterial and fungal strains, but have not been reported as an anti-QS agent. Therefore, the aim of present work was to show the computational analysis for the interaction of AgNPs with the QS system using an In silico approach...
2017: In Silico Pharmacology
Rafael Vincent M Manalo
In this study, the interactions of flavonoid, tannin and cardenolide moieties as well as their known metabolites were docked against the apolar NMR structure of the aggregatory amyloid-beta fragment (Aβ1-42 ). Results showed that the catechin moiety favorably bound Aβ1-42 peptide at Asp23, Asn27, Ser26 and Glu22 residues, with chalcone similarly binding the middle region of the peptide. Remarkably, hippuric and ferulic acids exhibited hydrophobic interactions with Aβ1-42 at the latter portion of the peptide, possibly blocking the salt bridges formed by Glu22-Lys28 which stabilizes Phe19-Gly25, as well as the β-sheet Leu34-Gly38 that are known to exist in peptide aggregation...
2017: In Silico Pharmacology
Ganapathi Thipparapu, Rajanna Ajumeera, Vijayalakshmi Venkatesan
Dihydropyrimidine derivatives possess many biological activities due to presence of pyrimidine ring structure in various nucleic acids, vitamins, coenzymes, uric acid and their derivatives. They have possessed broad spectrum actions like antibacterial, antifungal, antiviral, anticancer and antihypertensive etc. Before synthesis of compounds, it is good to predict biological activity using in silico methods. Here, we have selected some of N ( 3a - f ) and O ( 4a - f ) mannich bases of dihydro pyrimidine derivatives emphasized on histone deacetylase 4 (HDAC-4) inhibitions activity...
2017: In Silico Pharmacology
Radhakrishnan S Jisha, Lilly Aswathy, Vijay H Masand, Jayant M Gajbhiye, Indira G Shibi
This study focuses on understanding the structural features of 3,6-dihydroimidazo(4,5-d)pyrrolo(2,3-b)pyridin-2(1H)-one (dpp) derivatives to computationally identify new JAK inhibiting compounds. For the purpose, a novel virtual screening strategy, with 2D and 3D-QSAR (CoMFA and CoMSIA), data mining, pharmacophore modeling, ADMET prediction, multi-targeted protein-based docking and inverse QSAR, was employed. The 2D-QSAR equations developed for the JAK3, JAK2 and JAK1 involved five physicochemical descriptors...
2017: In Silico Pharmacology
David Morakinyo Sanni, Toluwase Hezekiah Fatoki, Ayodele Oluseyi Kolawole, Afolabi Clement Akinmoladun
Morinda citrifolia (Noni) fruit has a long history of dietary use in tropical regions of the world. Pharmacological properties that have been attributed to the fruit include anti-inflammatory, anti-cancer, and antioxidant properties. Xeronine, a small alkaloid which has been patented (US4543212) is one of the bioactive compounds of Noni fruit, which is believed to be capable of modifying the molecular structure of specific inactive proteins thereby regulating proper folding to active enzymes. Despite reports of the potential of Xeronine as therapeutic agent, its presence is controversial and its structure has not been explored...
2017: In Silico Pharmacology
Tabish Qidwai
Development of resistance in the Plasmodium falciparum to Artemisinin, the most effective anti-malarial compound, threatens malaria elimination tactics. To gain more efficacious Artemisinin derivatives, QSAR modeling and docking was performed. In the present study, 2D-QSAR model and molecular docking were used to evaluate the Artemisinin compounds and to reveal their binding modes and structural basis of inhibitory activity. Moreover, ADMET-related descriptors have been calculated to predict the pharmacokinetic properties of the effective compounds...
December 2016: In Silico Pharmacology
Anuradha Bhardwaj, Varij Nayan, Parvati Sharma, Sanjay Kumar, Yash Pal, Jitender Singh
Equine pituitary gonadotropins (eLH, eFSH, eCG) are heterodimeric glycoprotein hormones with alpha (α) and beta (β) subunits. It is responsible for maintenance of pregnancy in mares during early gestation and fairly valuable for inducing superovulation in animals other than equines. The alpha subunit is common, while beta subunit is species-specific in all glycoprotein hormones. In the present investigation, molecular cloning and in silico characterization including homology modeling and molecular docking analysis of the equine chorionic gonadotropin (eCG) alpha subunit was carried out for gaining structural and functional insights into the eCG alpha subunit and its possible interaction with ganirelix, a gonadotropin-releasing hormone (GnRH) antagonist...
December 2016: In Silico Pharmacology
Ashwini Khanderao Jadhav, Sankunny Mohan Karuppayil
DNA relaxation is an important step in DNA replication. DNA topoisomerases play a major role in DNA relaxation. Hence these enzymes are important targets for cancer drugs. DNA topoisomerase inhibitors bind to the transient enzyme-DNA complex and inhibit DNA replication. Various inhibitors of topoisomerase I and II are prescribed as drugs. Topoisomerase II is considered as an important target for the development of anticancer drugs. In this study we have demonstrated molecular docking of thirteen fluoroquinolines with human DNA topoisomerase II alpha (a) and beta (b)...
December 2016: In Silico Pharmacology
Dini Sri Damayanti, Didik Huswo Utomo, Chandra Kusuma
FOXO1 protein inactivation in the nucleus is one of targets for the treatment of diabetes mellitus. Annona muricata leaves contain flavonoid and phenolic compound alkaloids that were known to be able to increase pancreatic β cell proliferation in animal experiment. This research aimed to predict the active compound ability of the Annona muricata leaves to bind and inhibit FOXO1 protein through in silico study. Analysis of molecular docking was performed by using Autodock Vina PyRx. this research proved that anonaine, rutin, muricatocin a, isolaureline, xylopine, and kaempferol 3-O-rutinoside had an equal or smaller free binding energy compared to the control compound...
December 2016: In Silico Pharmacology
Maryam Golshani, Mana Oloomi, Saeid Bouzari
Shiga toxins belong to a family of structurally and functionally related toxins serving as the main virulence factors for pathogenicity of the Shiga toxin-producing Escherichia coli (STEC) associating with Hemolytic uremic syndrome (HUS). At present, there is no effective treatment or prevention for HUS. The aim of the present study was to find conserved regions within the amino acid sequences of Stx1, Stx2 (Shiga toxin) and their variants. In this regard, In-silico identification of conformational continuous B cell and T-cell epitopes was performed in order to introduce new potential vaccine candidates...
December 2016: In Silico Pharmacology
Shakhinur Islam Mondal, Zabed Mahmud, Montasir Elahi, Arzuba Akter, Nurnabi Azad Jewel, Md Muzahidul Islam, Sabiha Ferdous, Taisei Kikuchi
Protein-protein interaction (PPI) and host-pathogen interactions (HPI) proteomic analysis has been successfully practiced for potential drug target identification in pathogenic infections. In this research, we attempted to identify new drug target based on PPI and HPI computation approaches and subsequently design new drug against devastating enterohemorrhagic Escherichia coli O104:H4 C277-11 (Broad), which causes life-threatening food borne disease outbreak in Germany and other countries in Europe in 2011...
December 2016: In Silico Pharmacology
Monika Marczak, Krystyna Okoniewska, Tomasz Grabowski
BACKGROUND: Total body clearance of biological drugs is for the most part dependent on the receptor mechanisms (receptor mediated clearance) and the concentration of antibodies aimed at administered drug - anti-drug-antibodies (ADA). One of the significant factors that induces the increase of ADA level after drug administration could be the aggregates present in the finished product or formed in the organism. Numerous attempts have been made to identify the sequence fragments that could be responsible for forming the aggregates - aggregate prone regions (APR)...
December 2016: In Silico Pharmacology
Tahirah Yasmin, Salma Akter, Mouly Debnath, Akio Ebihara, Tsutomu Nakagawa, A H M Nurun Nabi
PURPOSE: Campylobacter jejuni is the one of the leading causes of bacterial diarrheal illness worldwide. This study aims to design specific epitopes for the utility of designing peptide vaccine(s) against C. jejuni by targeting invasive, virulent and membrane associated proteins like FlaA, Cia, CadF, PEB1, PEB3 and MOMP. METHODS: In the present study, various immunoinformatics approaches have been applied to design a potential epitope based vaccine against C. jejuni...
December 2016: In Silico Pharmacology
Jinhyuk Kim, Toru Nakamura, Yoshiharu Yamamoto
Many biomarkers from genetic, neuroimaging, and biological/biochemical measures have been recently developed in order to make a shift toward the objective evaluation of psychiatric disorders. However, they have so far been less successful in capturing dynamical changes or transitions in pathological states, such as those occurring during the course of clinical treatments or pathogenic processes of disorders. A momentary biomarker is now required for objective monitoring of such dynamical changes. The development of ecological momentary assessment (EMA) allows the assessment of dynamical aspects of diurnal/daily clinical conditions and subjective symptoms...
December 2016: In Silico Pharmacology
Elliot Offman, Colin Phipps, Andrea N Edginton
PURPOSE: Physiologically-based pharmacokinetic (PBPK) models provide a rational mechanistic approach for predicting the time course of macromolecules in plasma. Population PBPK models for large molecules necessitate incorporation of lymphatic circulation to mechanistically account for biodistribution. Moreover, characterization of subcutaneous absorption requires consideration of the microvascular transit from the injection site to the systemic circulation. A PBPK model for a pegylated peptide conjugate, previously developed for primates, was modified to describe the lymphatic uptake in a population of humans by incorporation of interindividual variability in the lymphatic circulation and a unique lymphatic drainage compartment (LDC)...
December 2016: In Silico Pharmacology
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