keyword
MENU ▼
Read by QxMD icon Read
search

ADME in silico

keyword
https://www.readbyqxmd.com/read/29658442/evaluation-of-in-silico-anti-parkinson-potential-of-%C3%AE-asarone
#1
Meenakshi Gupta, Kamal Kant, Ruchika Sharma, Anoop Kumar
INTRODUCTION: Parkinson's disease is affecting millions of people worldwide. The prevalence of Parkinson's disease is 0.3% globally, rising to 1% in more than 60 years of age and 4% in more than 80 years of age and the figures are thought to be doubled by 2030. Thus, there is a great need to identify novel therapeutic strategies or candidate drug molecule which can rescue neuronal degeneration. β-asarone has potential to act as a neuroprotective agent but regarding its role in Parkinson disease, very few reports are available...
April 16, 2018: Central Nervous System Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29627693/in-silico-evidences-for-binding-of-glucokinase-activators-to-egfr-c797s-to-overcome-egfr-resistance-obstacle-with-mutant-selective-allosteric-inhibition
#2
Harun Patel, Rahul Pawara, Sanjay Surana
The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are generally utilized as a part of patients with non-small cell lung carcinoma (NSCLC). However, EGFR T790M mutation results in resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation has been in active clinical development to triumph the resistance problem; they covalently bind with conserved Cys797 inside the EGFR active site, offering both potency and kinase-selectivity. Third generation drugs target C797, which makes the C797S resistance mutation more subtle...
March 29, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29596928/cardiac-safety-evaluation-in-zebrafish-and-in-silico-adme-prediction-of-cephalosporins-with-an-aminothiazoyl-ring-at-the-c-7-position
#3
Ying Han, Bo Chen, Jingpu Zhang, Changqin Hu
Systems toxicology approaches have been used as important tools in the drug discovery and medicine quality control processes. The aim of this study was to assess the pharmacokinetic and toxicity properties of cephalosporins with an aminothiazoyl ring at the C-7 position (CATRs). Cardiac toxicity of the compounds was assessed in zebrafish embryos, and it was determined that CATRs disturbed the formation and development of the heart in a dose-dependent manner. Differentially expressed genes (DEGs) related to the heart were also identified by transcriptome analysis, and co-DEGs were obtained in the protein-protein interaction (PPI) network...
March 26, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29595093/synergy-of-clavine-alkaloid-chanoclavine-with-tetracycline-against-multi-drug-resistant-e-coli
#4
Gaurav Raj Dwivedi, Anupam Maurya, Dharmendra Kumar Yadav, Vigyasa Singh, Feroz Khan, Mahendra Kumar Gupta, Mastan Singh, Mahendra P Darokar, Santosh Kumar Srivastava
The emergence of multidrug resistance (MDR) in Gram negative bacteria (GNB) and lack of novel classes of antibacterial agents have raised an immediate need to identify antibacterial agents, which can reverse the phenomenon of MDR. The purpose of present study was to evaluate synergy potential and understanding the drug resistance reversal mechanism of chanoclavine isolated from Ipomoea muricata against the multidrug resistant clinical isolate of Escherichia coli (MDREC). Although chanoclavine did not show antibacterial activity of its own, but in combination, it could reduce the minimum inhibitory concentration (MIC) of tetracycline (TET) up to 16 folds...
March 29, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29543339/fungal-biofilm-inhibition-by-piperazine-sulphonamide-linked-schiff-bases-design-synthesis-and-biological-evaluation
#5
Rajendra H Patil, Firoz A Kalam Khan, Kaivalya Jadhav, Manoj Damale, Siddique Akber Ansari, Hamad M Alkahtani, Azmat Ali Khan, Shantanu D Shinde, Rajesh Patil, Jaiprakash N Sangshetti
We report the synthesis of some new piperazine-sulphonamide linked Schiff bases as fungal biofilm inhibitors with antibacterial and antifungal potential. The biofilm inhibition result of Candida albicans proposed that the compounds 6b (IC50  = 32.1 μM) and 6j (IC50  = 31.4 μM) showed higher inhibitory activity than the standard fluconazole (IC50  = 40 μM). Compound 6d (MIC = 26.1 μg/mL) with a chloro group at the para position was found to be the most active antibacterial agent of the series against Bacillus subtilis when compared with the standard ciprofloxacin (MIC = 50 μg/mL)...
March 15, 2018: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29526583/identifying-potential-quality-markers-of-xin-su-ning-capsules-acting-on-arrhythmia-by-integrating-uhplc-ltq-orbitrap-adme-prediction-and-network-target-analysis
#6
Rui Guo, Xiaoxiao Zhang, Jin Su, Haiyu Xu, Yanqiong Zhang, Fangbo Zhang, Defeng Li, Yi Zhang, Xuefeng Xiao, Shuangcheng Ma, Hongjun Yang
BACKGROUND: Quality marker (Q-markers) has been proposed as a novel concept for quality evaluation and standard elaboration of traditional Chinese medicine (TCM). Xin-Su-Ning capsule (XSNC) has been extensively used for the treatment of arrhythmia with the satisfactory therapeutic effects in clinics. However, it is lack of reliable and effective Q-markers of this prescription. PURPOSE: To identify potential Q-markers of XSNC against arrhythmia. STUDY DESIGN: An integrative pharmacology-based investigation was performed...
February 10, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29522642/pyridine-substituted-thiazolylphenol-derivatives-synthesis-modeling-studies-aromatase-inhibition-and-antiproliferative-activity-evaluation
#7
Merve Ertas, Zafer Sahin, Barkin Berk, Leyla Yurttas, Sevde N Biltekin, Seref Demirayak
Drugs used in breast cancer treatments target the suppression of estrogen biosynthesis. During this suppression, the main goal is to inhibit the aromatase enzyme that is responsible for the cyclization and structuring of estrogens either with steroid or non-steroidal-type inhibitors. Non-steroidal derivatives generally have a planar aromatic structure attached to the triazole ring system in their structures, which inhibits hydroxylation reactions during aromatization by coordinating the heme group. Bioisosteric replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase the selectivity for aromatase enzyme inhibition...
March 9, 2018: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29475176/rational-design-of-methicillin-resistance-staphylococcus-aureus-inhibitors-through-3d-qsar-molecular-docking-and-molecular-dynamics-simulations
#8
Srilata Ballu, Ramesh Itteboina, Sree Kanth Sivan, Vijjulatha Manga
Staphylococcus aureus is a gram positive bacterium. It is the leading cause of skin and respiratory infections, osteomyelitis, Ritter's disease, endocarditis, and bacteraemia in the developed world. We employed combined studies of 3D QSAR, molecular docking which are validated by molecular dynamics simulations and in silico ADME prediction have been performed on Isothiazoloquinolones inhibitors against methicillin resistance Staphylococcus aureus. Three-dimensional quantitative structure-activity relationship (3D-QSAR) study was applied using comparative molecular field analysis (CoMFA) with Q2 of 0...
December 20, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29454190/potholing-of-the-hydrophobic-heme-oxygenase-1-western-region-for-the-search-of-potent-and-selective-imidazole-based-inhibitors
#9
Loredana Salerno, Emanuele Amata, Giuseppe Romeo, Agostino Marrazzo, Orazio Prezzavento, Giuseppe Floresta, Valeria Sorrenti, Ignazio Barbagallo, Antonio Rescifina, Valeria Pittalà
Here we report the design, synthesis, and molecular modeling of new potent and selective imidazole-based HO-1 inhibitors in which the imidazole nucleus and the hydrophobic groups are linked by a phenylethanolic spacer. Most of the tested compounds showed a good inhibitor activity with IC 50 values in the low micromolar range, with two of them (1b and 1j) exhibiting also high selectivity toward HO-2. These results were obtained by the idea of potholing the entire volume of the principal hydrophobic western region with an appropriate ligand volume...
February 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29449587/the-mechanisms-of-bushen-yizhi-formula-as-a-therapeutic-agent-against-alzheimer-s-disease
#10
Haobin Cai, Yunxia Luo, Xin Yan, Peng Ding, Yujie Huang, Shuhuan Fang, Rong Zhang, Yunbo Chen, Zhouke Guo, Jiansong Fang, Qi Wang, Jun Xu
Bushen-Yizhi prescription (BSYZ) has been an effective traditional Chinese medicine (TCM) prescription in treating Alzheimer's disease (AD) for hundreds of years. However, the underlying mechanisms have not been fully elucidated yet. In this work, a systems pharmacology approach was developed to reveal the underlying molecular mechanisms of BSYZ in treating AD. First, we obtained 329 candidate compounds of BSYZ by in silico ADME/T filter analysis and 138 AD-related targets were predicted by our in-house WEGA algorithm via mapping predicted targets into AD-related proteins...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29429576/in-silico-studies-synthesis-and-pharmacological-evaluation-to-explore-multi-targeted-approach-for-imidazole-analogues-as-potential-cholinesterase-inhibitors-with-neuroprotective-role-for-alzheimer-s-disease
#11
Archana S Gurjar, Mrunali N Darekar, Keng Yoon Yeong, Luyi Ooi
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with multiple factors associated with its pathogenesis. Our strategy against AD involves design of multi-targeted 2-substituted-4,5-diphenyl-1H-imidazole analogues which can interact and inhibit AChE, thereby, increasing the synaptic availability of ACh, inhibit BuChE, relieve induced oxidative stress and confer a neuroprotective role. Molecular docking was employed to study interactions within the AChE active site. In silico ADME study was performed to estimate pharmacokinetic parameters...
February 2, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29421570/design-synthesis-and-pharmacological-evaluation-of-n-benzyl-piperidinyl-aryl-acylhydrazone-derivatives-as-donepezil-hybrids-discovery-of-novel-multi-target-anti-alzheimer-prototype-drug-candidates
#12
Flávia Pereira Dias Viegas, Matheus de Freitas Silva, Miguel Divino da Rocha, Maísa Rosa Castelli, Mariana Máximo Riquiel, Rafael Pereira Machado, Sarah Macedo Vaz, Laís Medeiros Simões de Lima, Karla Cristine Mancini, Patrícia Cruz Marques de Oliveira, Élida Parreira Morais, Vanessa Silva Gontijo, Fernanda Motta R da Silva, Dora D'Alincourt da Fonseca Peçanha, Newton Gonçalves Castro, Gilda A Neves, Alexandre Giusti-Paiva, Fabiana Cardoso Vilela, Lidiane Orlandi, Ihosvany Camps, Márcia Paranho Veloso, Luis Felipe Leomil Coelho, Marisa Ionta, Guilherme Álvaro Ferreira-Silva, Rodrigo Machado Pereira, Laurent E Dardenne, Isabella Alvim Guedes, Wellerson de Oliveira Carneiro Junior, Paula Maria Quaglio Bellozi, Antônio Carlos Pinheiro de Oliveira, Fábio Furlan Ferreira, Letizia Pruccoli, Andrea Tarozzi, Claudio Viegas
A new series of sixteen multifunctional N-benzyl-piperidine-aryl-acylhydrazones hybrid derivatives was synthesized and evaluated for multi-target activities related to Alzheimer's disease (AD). The molecular hybridization approach was based on the combination, in a single molecule, of the pharmacophoric N-benzyl-piperidine subunit of donepezil, the substituted hydroxy-piperidine fragment of the AChE inhibitor LASSBio-767, and an acylhydrazone linker, a privileged structure present in a number of synthetic aryl- and aryl-acylhydrazone derivatives with significant AChE and anti-inflammatory activities...
January 31, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29380627/the-benefits-of-in-silico-modeling-to-identify-possible-small-molecule-drugs-and-their-off-target-interactions
#13
Mire Zloh, Stewart B Kirton
The research into the use of small molecules as drugs continues to be a key driver in the development of molecular databases, computer-aided drug design software and collaborative platforms. The evolution of computational approaches is driven by the essential criteria that a drug molecule has to fulfill, from the affinity to targets to minimal side effects while having adequate absorption, distribution, metabolism, and excretion (ADME) properties. A combination of ligand- and structure-based drug development approaches is already used to obtain consensus predictions of small molecule activities and their off-target interactions...
January 30, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29373271/synthesis-biological-evaluation-and-docking-study-of-a-new-series-of-di-substituted-benzoxazole-derivatives-as-selective-cox-2-inhibitors-and-anti-inflammatory-agents
#14
Avneet Kaur, Dharam P Pathak, Vidushi Sharma, Sharad Wakode
A new series of substituted-N-(3,4-dimethoxyphenyl)-benzoxazole derivatives 13a-13p was synthesized and evaluated in vitro for their COX (I and II) inhibitory activity, in vivo anti-inflammatory and ulcerogenic potential. Compounds 13d, 13h, 13k, 13l and 13n exhibited significant COX-2 inhibitory activity and selectivity towards COX-2 over COX-1. These selected compounds were screened for their in vivo anti-inflammatory activity by carrageenan induced rat paw edema method. Among these compounds, 13d was the most promising analogs of the series with percent inhibition of 84...
January 11, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29274684/identification-of-novel-nt-mgam-inhibitors-for-potential-treatment-of-type-2-diabetes-virtual-screening-atom-based-3d-qsar-model-docking-analysis-and-adme-study
#15
Aicha Laoud, Fouad Ferkous, Laura Maccari, Giorgio Maccari, Youcef Saihi, Khaireddine Kraim
In this study, a virtual screening procedure was applied to identify new potential nt-MGAM inhibitors as a possible medication for type 2 diabetes. To this aim, a series of salacinol analogues were first investigated by docking analysis for their binding to the X-ray structure of the biological target nt-MGAM. Key interactions for ligand binding into the receptor active site were identified which shared common features to those found for other known inhibitors, which strengthen the results of this study. 3D QSAR model was then built and showed to be statistically significant and with a good predictive power for the training (R2  = 0...
February 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29258770/microwave-assisted-synthesis-of-novel-5-substituted-benzylidene-amino-2-butyl-benzofuran-3-yl-4-methoxyphenyl-methanones-as-antileishmanial-and-antioxidant-agents
#16
Sanjeev R Patil, Satyanarayana Bollikonda, Rajendra H Patil, Jaiprakash N Sangshetti, Anil S Bobade, Ashish Asrondkar, Padi Pratap Reddy, Devanand B Shinde
A series of 5-substitutedbenzylideneamino-2-butylbenzofuran-3-yl-4-methoxyphenyl methanones is synthesized and evaluated for antileishmanial and antioxidant activities. Compounds 4f (IC50  = 52.0 ± 0.09 µg/ml), 4h (IC50  = 56.0 ± 0.71 µg/ml) and 4l (IC50  = 59.3 ± 0.55 µg/ml) were shown significant antileishmanial when compared with standard sodium stibogluconate (IC50  = 490.0 ± 1.5 µg/ml). Antioxidant study revealed that compounds 4i (IC50  = 2.44 ± 0...
December 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29078760/in-silico-repurposing-of-antipsychotic-drugs-for-alzheimer-s-disease
#17
Shivani Kumar, Suman Chowdhury, Suresh Kumar
BACKGROUND: Alzheimer's disease (AD) is the most prevalent form of dementia and represents one of the highest unmet requirements in medicine today. There is shortage of novel molecules entering into market because of poor pharmacokinetic properties and safety issues. Drug repurposing offers an opportunity to reinvigorate the slowing drug discovery process by finding new uses for existing drugs. The major advantage of the drug repurposing approach is that the safety issues are already investigated in the clinical trials and the drugs are commercially available in the marketplace...
October 27, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/29077483/risk-of-late-onset-alzheimer-s-disease-by-plasma-cholesterol-rational-in-silico-drug-investigation-of-pyrrole-based-hmg-coa-reductase-inhibitors
#18
Sajad Shahbazi, Jagdeep Kaur, Ananya Kuanar, Dattatreya Kar, Shikha Singh, Ranbir Chander Sobti
Alzheimer's disease (AD), a worldwide renowned progressive neurodegenerative disorder, is the most common cause of dementia. There are several studies on the important role of cholesterol metabolism in AD pathogenesis, which indicated that the high concentrations of serum cholesterol increase the risk of AD. Biosynthesis of the plasma cholesterol and other isoprenoids is catalyzed by 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) through the conversion of HMG-CoA to mevalonic acid in mevalonate pathway. Normally, the high level of plasma cholesterol is downregulated by HGMCR inhibition as the result of degradation of LDL, but in abnormal conditions, for example, high blood glucose, the HMGCR over activated resulting in uncontrolled blood cholesterol...
October 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/29065322/sulfonyl-hydrazones-derived-from-3-formylchromone-as-non-selective-inhibitors-of-mao-a-and-mao-b-synthesis-molecular-modelling-and-in-silico-adme-evaluation
#19
Syed Mobasher Ali Abid, Hafiza Amna Younus, Mariya Al-Rashida, Zunaira Arshad, Tooba Maryum, Mazhar Amjad Gilani, Abdulrahman I Alharthi, Jamshed Iqbal
A series of sulfonyl hydrazones derived from 3-formylchromone was synthesized and discovered to be effective, non-selective inhibitors of monoamine oxidases (MAO-A and MAO-B). The compounds are easily (synthetically) accessible in high yields, by simple condensation of 4-methylbenzenesulfonohydrazide with different (un)substituted 3-formylchromones. All compounds had IC50 values in lower micro-molar range (IC50 = 0.33-7.14 μM for MAO-A, and 1.12-3.56 μM for MAO-B). The most active MAO-B inhibitor was N'-[(E)-(6-fluoro-4-oxo-4H-chromen-3-yl)methylidene]-4-methylbenzenesulfonohydrazide (3e) with IC50 value of 1...
October 4, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29056366/natural-modulators-of-nonalcoholic-fatty-liver-disease-mode-of-action-analysis-and-in-silico-adme-tox-prediction
#20
Merilin Al Sharif, Petko Alov, Vessela Vitcheva, Antonia Diukendjieva, Mattia Mori, Bruno Botta, Ivanka Tsakovska, Ilza Pajeva
Nonalcoholic fatty liver disease (NAFLD) is considered to be the most common chronic liver disease. The discovery of natural product-based NAFLD modulators requires a more comprehensive study of their modes of action (MoAs). In this study we analysed available in the literature data for 26 naturally-derived compounds associated with experimental evidence for NAFLD alleviation and outlined potential biomolecular targets and a network of pharmacological MoAs for 12 compounds with the highest number of experimentally supported MoA key events, modulated by them...
December 15, 2017: Toxicology and Applied Pharmacology
keyword
keyword
109333
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"