keyword
MENU ▼
Read by QxMD icon Read
search

ADME in silico

keyword
https://www.readbyqxmd.com/read/28803043/structure-based-development-of-novel-triazoles-and-related-thiazolotriazoles-as-anticancer-agents-and-cdc25a-b-phosphatase-inhibitors-synthesis-in%C3%A2-vitro-biological-evaluation-molecular-docking-and-in-silico-adme-t-studies
#1
Sherif A F Rostom, Mona H Badr, Heba A Abd El Razik, Hayam M A Ashour
Synthesis of twenty nine new 1,2,4-triazoles and some derived thiazolothiadiazoles (structurally-relevant to some reported triazoles with anticancer and/or Cdc25A/B inhibitory activities) is described in this study. The obtained NCI's in vitro antitumor data revealed that five analogs (12, 15, 18, 19 and 22) displayed considerable tumor percentage growth inhibitory activity (GI%), among which the analog 18 possessed a special antitumor potential and spectrum. Additionally, the same five analogs showed a marginal GI effect on the normal breast epithelial cell line MCF-10A indicating higher selectivity towards cancer cells...
July 25, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28802226/taraxerol-a-pentacyclic-triterpenoid-from-abroma-augusta-leaf-attenuates-diabetic-nephropathy-in-type-2-diabetic-rats
#2
Ritu Khanra, Niloy Bhattacharjee, Tarun K Dua, Ashis Nandy, Achintya Saha, Jatin Kalita, Prasenjit Manna, Saikat Dewanjee
Persistent hyperglycaemia coupled with inflammation plays an important role in the pathogenesis of diabetic nephropathy (DN). Present study examined the therapeutic potential of taraxerol isolated from the methanol extract of Abroma augusta leaf against DN using rodent model of type 2 diabetes (T2D). T2D was experimentally induced by high fat diet and a single low-single dose of streptozotocin (35mg/kg, i.p.). Accumulation of serum creatinine, urea, and uric acid, activation of lactate dehydrogenase and creatinin kinase, and release of urinary albumin represented the glomerular damage and the progression of nephropathy in T2D rats...
August 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28796406/diarylpyrazole-ligated-dihydropyrimidine-hybrids-as-potent-non-classical-antifolates-and-their-efficacy-against-plasmodium-falciparum
#3
Jaimin D Bhatt, Chaitanya J Chudasama, Kanuprasad D Patel
A series of diarylpyrazole clubbed dihydropyrimidine derivatives (J1-J30) was synthesized under microwave-assisted heating conditions by employing Biginelli reaction methodology and utilizing triethylammonium acetate both as a catalyst and as reaction medium, leading towards a greener reaction pathway. The synthesized entities were screened for their antimalarial efficacy against a Plasmodium falciparum strain in vitro. The active entities (J9, J15, J21, J25, and J27) obtained out of the in vitro screening were further evaluated for their enzyme inhibitory potency against the Pf-DHFR enzyme in vitro as well as in silico using Glide...
August 10, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28758238/design-synthesis-and-docking-study-of-pyrimidine-triazine-hybrids-for-gaba-estimation-in-animal-epilepsy-models
#4
Meeta Sahu, Nadeem Siddiqui, Mohd Javed Naim, Ozair Alam, Mohammad Shahar Yar, Vidushi Sharma, Sharad Wakode
A series of new pyrimidine-triazine hybrids (4a-t) was designed and synthesized, from which potent anticonvulsant agents were identified. Most of the compounds exhibited promising anticonvulsant activity against the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests, along with minimal motor impairment with higher safety compared to the standard drugs, phenytoin and carbamazepine. In the series, 5-(4-(4-fluorophenyl)-6-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4o) and 5-(6-(4-hydroxy-3-methoxyphenyl)-4-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4s) emerged as most potent anticonvulsant agents with median doses of 22...
July 31, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28746940/comparison-of-the-skin-penetration-of-3-metabolically-stable-chemicals-using-fresh-and-frozen-human-skin
#5
Carine Jacques-Jamin, Hélène Duplan, Helga Rothe, Ophelie Vaillant, Joan Eilstein, Sebastien Grégoire, Richard Cubberley, Daniela Lange, Corie Ellison, Martina Klaric, Nicola Hewitt, Andreas Schepky
BACKGROUND: The Cosmetics Europe ADME Task Force is developing in vitro and in silico tools for predicting skin and systemic concentrations after topical application of cosmetic ingredients. There are conflicting reports as to whether the freezing process affects the penetration of chemicals; therefore, we evaluated whether the storage of human skin used in our studies (8-12 weeks at -20°C) affected the penetration of model chemicals. METHODS: Finite doses of trans-cinnamic acid (TCA), benzoic acid (BA), and 6-methylcoumarin (6MC) (non-volatile, non-protein reactive and metabolically stable in skin) were applied to fresh and thawed frozen skin from the same donors...
July 27, 2017: Skin Pharmacology and Physiology
https://www.readbyqxmd.com/read/28743970/adme-space-a-new-tool-for-medicinal-chemists-to-explore-adme-properties
#6
Giovanni Bocci, Emanuele Carosati, Philippe Vayer, Alban Arrault, Sylvain Lozano, Gabriele Cruciani
We introduce a new chemical space for drugs and drug-like molecules, exclusively based on their in silico ADME behaviour. This ADME-Space is based on self-organizing map (SOM) applied to 26,000 molecules. Twenty accurate QSPR models, describing important ADME properties, were developed and, successively, used as new molecular descriptors not related to molecular structure. Applications include permeability, active transport, metabolism and bioavailability studies, but the method can be even used to discuss drug-drug interactions (DDIs) or it can be extended to additional ADME properties...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708399/development-and-validation-of-a-computational-model-ensemble-for-the-early-detection-of-bcrp-abcg2-substrates-during-the-drug-design-stage
#7
Melisa Edith Gantner, Roxana Noemí Peroni, Juan Francisco Morales, María Luisa Villalba, María Esperanza Ruiz, Alan Talevi
Breast Cancer Resistance Protein (BCRP) is an ATP-dependent efflux transporter linked to the multidrug resistance phenomenon in many diseases such as epilepsy and cancer, and a potential source of drug interactions. For those reasons, the early identification of substrates and non-substrates of this transporter during the drug discovery stage is of great interest. We have developed a computational non-linear model ensemble based on conformational independent molecular descriptors using a combined strategy of genetic algorithms, J48 decision tree classifiers and data fusion...
July 14, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28694764/2-pyrazoline-derivatives-in-neuropharmacology-synthesis-adme-prediction-molecular-docking-and-in-vivo-biological-evaluation
#8
Savita Upadhyay, Avinash C Tripathi, Sarvesh Paliwal, Shailendra K Saraf
A novel series of 1,3,5-trisubstituted-2-pyrazoline derivatives (PFC-1 to PFC-16) were synthesized in a three step reaction using conventional and microwave assisted green chemistry approach. The synthesized derivatives were characterized and their chemical structures were established by various physicochemical methods such as IR, Mass, (1)H-NMR, (13)C-NMR and elemental analysis. The synthesized compounds were tested for their neuropharmacological potential. The compounds exhibited significant antidepressant and anti-anxiety activities against various behavioral in vivo models...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28693910/antileishmanial-potential-of-fused-5-pyrazin-2-yl-4h-1-2-4-triazole-3-thiols-synthesis-biological-evaluations-and-computational-studies
#9
Sanjeev R Patil, Ashish Asrondkar, Vrushali Patil, Jaiprakash N Sangshetti, Firoz A Kalam Khan, Manoj G Damale, Rajendra H Patil, Anil S Bobade, Devanand B Shinde
A series of newer 1,2,4-triazole-3-thiol derivatives 5(a-m) and 6(a-i) containing a triazole fused with pyrazine moiety of pharmacological significance have been synthesized. All the synthesized compounds were screened for their in vitro antileishmanial and antioxidant activities. Compounds 5f (IC50=79.0µM) and 6f (IC50=79.0µM) were shown significant antileishmanial activity when compared with standard sodium stibogluconate (IC50=490.0µM). Compounds 5b (IC50=13.96µM) and 6b (IC50=13.96µM) showed significant antioxidant activity...
June 22, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28655656/lessons-learned-from-read-across-case-studies-for-repeated-dose-toxicity
#10
Terry W Schultz, Mark T D Cronin
A series of case studies designed to further acceptance of read-across predictions, especially for chronic health-related endpoints, have been evaluated with regard to the knowledge and insight they provide. A common aim of these case studies was to examine sources of uncertainty associated with read-across. While uncertainty is related to the quality and quantity of the read across endpoint data, uncertainty also includes a variety of other factors, the foremost of which is uncertainty associated with the justification of similarity and quantity and quality of data for the source chemical(s)...
June 24, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28636542/niaoduqing-granules-relieve-chronic-kidney-disease-symptoms-by-decreasing-renal-fibrosis-and-anemia
#11
Xu Wang, Suyun Yu, Qi Jia, Lichuan Chen, Jinqiu Zhong, Yanhong Pan, Peiliang Shen, Yin Shen, Siliang Wang, Zhonghong Wei, Yuzhu Cao, Yin Lu
NiaoDuQing (NDQ) granules, a traditional Chinese medicine, has been clinically used in China for over fourteen years to treat chronic kidney disease (CKD). To elucidate the mechanisms underlying the therapeutic benefits of NDQ, we designed an approach incorporating chemoinformatics, bioinformatics, network biology methods, and cellular and molecular biology experiments. A total of 182 active compounds were identified in NDQ granules, and 397 putative targets associated with different diseases were derived through ADME modelling and target prediction tools...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28628860/in-silico-modeling-on-adme-properties-of-natural-products-classification-models-for-blood-brain-barrier-permeability-its-application-to-traditional-chinese-medicine-and-in-vitro-experimental-validation
#12
Xiuqing Zhang, Ting Liu, Xiaohui Fan, Ni Ai
In silico modeling of blood-brain barrier (BBB) permeability plays an important role in early discovery of central nervous system (CNS) drugs due to its high-throughput and cost-effectiveness. Natural products (NP) have demonstrated considerable therapeutic efficacy against several CNS diseases. However, BBB permeation property of NP is scarcely evaluated both experimentally and computationally. It is well accepted that significant difference in chemical spaces exists between NP and synthetic drugs, which calls into doubt on suitability of available synthetic chemical based BBB permeability models for the evaluation of NP...
June 7, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28609624/in-silico-absorption-distribution-metabolism-excretion-and-pharmacokinetics-adme-pk-utility-and-best-practices-an-industry-perspective-from-the-international-consortium-for-innovation-through-quality-in-pharmaceutical-development
#13
Franco Lombardo, Prashant V Desai, Rieko Arimoto, Kelly E Desino, Holger Fischer, Christopher E Keefer, Carl Petersson, Susanne Winiwarter, Fabio Broccatelli
In silico tools to investigate absorption, distribution, metabolism, excretion and pharmacokinetics (ADME-PK) properties of new chemical entities are an integral part of the current industrial drug discovery paradigm. While many companies are active in the field, scientists engaged in this area don't necessarily share the same background and have limited resources when seeking guidance on how to initiate and maintain an in silico ADME-PK infrastructure in an industrial setting. This work summarizes the views of a group of industrial in silico and experimental ADME scientists, participating in the In Silico ADME Working Group, a subgroup of the International Consortium for Innovation through Quality in Pharmaceutical Development (IQ) Drug Metabolism Leadership Group...
June 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28595533/recent-advances-of-computational-modeling-for-predicting-drug-metabolism-a-perspective
#14
Supratik Kar, Jerzy Leszczynski
Absorption, Distribution, Metabolism, Excretion (ADME) properties along with drug induced adverse effects are the major reasons for the late stage failure of drug candidates as well as cause for the expensive withdrawal of many approved drugs from the market. Considering adverse effects of drugs, metabolism factor has great importance in medicinal chemistry and clinical pharmacology because it influences the deactivation, activation, detoxification and toxification of drugs. Computational methods are effective approaches to reduce the number of safety issues by analyzing possible links between chemical structures and metabolism followed by adverse effects, as they serve the integration of information on several levels to enhance the reliability of outcomes...
June 6, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28579399/prevention-of-icaa-regulated-poly-n-acetyl-glucosamine-formation-in-staphylococcus-aureus-biofilm-through-new-drug-like-inhibitors-in-silico-approach-and-md-simulation-study
#15
Ayushi Gupta, Swechha Mishra, Sangeeta Singh, Sonali Mishra
OBJECTIVES: The effectiveness of various ligands against the protein structure of IcaA of the IcaABCD gene locus of Staphylococcus aureus were examined using the approach of structure based drug designing in reference with the protein's efficiency to form biofilms. RESULTS: Four compounds CID42738592, CID90468752, CID24277882, and CID6435208 were secluded from a database of 31,242 inhibitory ligands on the justification of the evaluated values falling under the four - tier structure based virtual screening...
June 1, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28549802/design-synthesis-and-biological-evaluation-of-novel-androst-3-5-diene-3-carboxylic-acid-derivatives-as-inhibitors-of-5%C3%AE-reductase-type-1-and-2
#16
Kejing Lao, Jie Sun, Chong Wang, Weiting Lyu, Boshen Zhou, Ruheng Zhao, Qian Xu, Qidong You, Hua Xiang
5α-Reductase is a key enzyme responsible for dihydrotestosterone biosynthesis and has been recognized as an important target for discovering new drugs against benign prostatic hyperplasia (BPH). In this study, a series of novel steroidal androst-3,5-diene-3-carboxylic acids have been designed and synthesized. Biological evaluations were performed on their 5α-reductase inhibitory activities by both in vitro enzyme inhibition assay and in vivo by prostate weighing method. Results showed that most of them displayed excellent 5α-reductase inhibitory potency...
May 24, 2017: Steroids
https://www.readbyqxmd.com/read/28544494/4-substituted-thieno-2-3-d-pyrimidines-as-potent-antibacterial-agents-rational-design-microwave-assisted-synthesis-biological-evaluation-and-molecular-docking-studies
#17
Rupinder K Gill, Harpreet Singh, Tilak Raj, Anuradha Sharma, Gagandeep Singh, Jitender Bariwal
In an attempt to discover a new class of antibacterial agents with improved efficacy and to overcome the drug resistant problems, some novel 4-substituted thieno[2,3-d]pyrimidines have been synthesized via microwave assisted methodology and evaluated for their in vitro antibacterial activity against various pathogenic bacterial strains. Compounds 12b and 13c showed the promising inhibitory potencies against S. aureus, B. subtilis, P. aeruginosa and E. coli with MICs ranging from 2 to 10 μg/ml. Compound 13c was also found to be highly potent against methicillin resistant S...
May 23, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28533752/protocatechuic-acid-a-phenolic-from-sansevieria-roxburghiana-leaves-suppresses-diabetic-cardiomyopathy-via-stimulating-glucose-metabolism-ameliorating-oxidative-stress-and-inhibiting-inflammation
#18
Niloy Bhattacharjee, Tarun K Dua, Ritu Khanra, Swarnalata Joardar, Ashis Nandy, Achintya Saha, Vincenzo De Feo, Saikat Dewanjee
Persistent hyperglycemia, impairment of redox status and establishment of inflammatory pathophysiology integrally play important role in the pathogenesis of diabetic cardiomyopathy (DC). Present study examined the therapeutic potential of protocatechuic acid isolated from the Sansevieria roxburghiana rhizomes against DC employing rodent model of type 2 diabetes (T2D). T2D was induced by high fat diet + a low-single dose of streptozotocin (35 mg/kg, i.p.). T2D rats exhibited significantly (p < 0.01) high fasting blood glucose level...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28529482/mode-of-action-analyses-of-neferine-a-bisbenzylisoquinoline-alkaloid-of-lotus-nelumbo-nucifera-against-multidrug-resistant-tumor-cells
#19
Onat Kadioglu, Betty Y K Law, Simon W F Mok, Su-Wei Xu, Thomas Efferth, Vincent K W Wong
Neferine, a bisbenzylisoquinoline alkaloid isolated from the green seed embryos of Lotus (Nelumbo nucifera Gaertn), has been previously shown to have various anti-cancer effects. In the present study, we evaluated the effect of neferine in terms of P-glycoprotein (P-gp) inhibition via in vitro cytotoxicity assays, R123 uptake assays in drug-resistant cancer cells, in silico molecular docking analysis on human P-gp and in silico absorption, distribution, metabolism, and excretion (ADME), quantitative structure activity relationships (QSAR) and toxicity analyses...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28526475/identification-and-preliminary-structure-activity-relationships-of-1-indanone-derivatives-as-novel-indoleamine-2-3-dioxygenase-1-ido1-inhibitors
#20
Dingding Gao, Yingxia Li
Indoleamine 2,3-dioxygenase 1 (IDO1) plays a vital role in the catabolism of tryptophan along with the kynurenine pathway which is involved in many human diseases including cancer, Alzheimer's disease, etc. In this study, compound 1 bearing a 1-Indanone scaffold was identified as a novel IDO1 inhibitor by structure-based virtual screening, with moderate to good enzymatic and cellular inhibitory activities. Also, surface plasmon resonance analysis validated the direct interaction between compound 1 and IDO1 protein...
May 10, 2017: Bioorganic & Medicinal Chemistry
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"