MolFind2: A Protocol for Acquiring and Integrating MS3 Data to Improve In Silico Chemical Structure Elucidation for Metabolomics

2019 ◽  
pp. 283-295
Author(s):  
Milinda A. Samaraweera ◽  
Dennis W. Hill ◽  
David F. Grant
Keyword(s):  
In Silico ◽  
Structure Elucidation ◽  
Chemical Structure

scholarly journals Development of an in silico prediction system of human renal excretion and clearance from chemical structure information incorporating fraction unbound in plasma as a descriptor

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Reiko Watanabe ◽  
Rikiya Ohashi ◽  
Tsuyoshi Esaki ◽  
Hitoshi Kawashima ◽  
Yayoi Natsume-Kitatani ◽  
...  
Keyword(s):  
Renal Clearance ◽  
In Silico ◽  
Regression Models ◽  
Chemical Structure ◽  
Prediction Models ◽  
Renal Excretion ◽  
Early Stage ◽  
Classification Model ◽  
Prediction System ◽  
Structure Information

AbstractPrediction of pharmacokinetic profiles of new chemical entities is essential in drug development to minimize the risks of potential withdrawals. The excretion of unchanged compounds by the kidney constitutes a major route in drug elimination and plays an important role in pharmacokinetics. Herein, we created in silico prediction models of the fraction of drug excreted unchanged in the urine (fe) and renal clearance (CLr), with datasets of 411 and 401 compounds using freely available software; notably, all models require chemical structure information alone. The binary classification model for fe demonstrated a balanced accuracy of 0.74. The two-step prediction system for CLr was generated using a combination of the classification model to predict excretion-type compounds and regression models to predict the CLr value for each excretion type. The accuracies of the regression models increased upon adding a descriptor, which was the observed and predicted fraction unbound in plasma (fu,p); 78.6% of the samples in the higher range of renal clearance fell within 2-fold error with predicted fu,p value. Our prediction system for renal excretion is freely available to the public and can be used as a practical tool for prioritization and optimization of compound synthesis in the early stage of drug discovery.

scholarly journals Ubiquitin-Proteasome Modulating Dolabellanes and Secosteroids from Soft Coral Clavularia flava

Marine Drugs ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 39
Author(s):  
Che-Yen Chiu ◽  
Xue-Hua Ling ◽  
Shang-Kwei Wang ◽  
Chang-Yih Duh
Keyword(s):  
Inhibitory Activity ◽  
Structure Elucidation ◽  
Chemical Structure ◽  
Soft Coral ◽  
Proteasome Inhibitors ◽  
Proteasome Inhibition ◽  
Structural Elucidation ◽  
Bioactive Molecules ◽  
High Content Screening ◽  
Ubiquitin Proteasome

We performed a high-content screening (HCS) assay aiming to discover bioactive molecules with proteasome inhibitory activity. By structural elucidation, we identified six compounds purified from soft coral Clavularia flava, which potentiates proteasome inhibition. Chemical structure elucidation revealed they are dolabellane- and secosteroid-based compounds including a new dolabellane, clavinflol C (1), three known dolabellanes, stolonidiol (2), stolonidiol-17-acetate (3), and clavinflol B (4) as well as two new secosteroids, 3β,11-dihydroxy-24-methyl-9,11-secocholest-5-en-9,23-dione (5) and 3β,11-dihydroxy-24-methylene-9,11-secocholest-5-en-9,23-dione (6). All six compounds show less cytotoxicity than those of known proteasome inhibitors, bortezomib and MG132. In summary, the high-content measurements of control inhibitors, bortezomib and MG132, manifest the highest ratio >2 in high-content measurement. Of the isolated compounds, 2 and 5 showed higher activity, followed by 3 and 6, and then 1 and 4 exhibited moderate inhibition.

scholarly journals Impact of Chemical Structure on Conjunctival Drug Permeability: Adopting Porcine Conjunctiva and Cassette Dosing for Construction of In Silico Model

2017 ◽  
Vol 106 (9) ◽  
pp. 2463-2471 ◽  
Author(s):  
Eva Ramsay ◽  
Marika Ruponen ◽  
Théo Picardat ◽  
Unni Tengvall ◽  
Marjo Tuomainen ◽  
...  
Keyword(s):  
In Silico ◽  
Chemical Structure ◽  
Drug Permeability ◽  
In Silico Model ◽  
Cassette Dosing

Chemical structure elucidation of total lignins in woods. Part II: Analysis of a fraction of residual wood left after MWL isolation and solubilized in lithium chloride/N,N-dimethylacetamide

Holzforschung ◽  
2006 ◽  
Vol 60 (6) ◽  
pp. 653-658 ◽  
Author(s):  
Hiroyuki Furuno ◽  
Toshiyuki Takano ◽  
Shuichi Hirosawa ◽  
Hiroshi Kamitakahara ◽  
Fumiaki Nakatsubo
Keyword(s):  
Lithium Chloride ◽  
Structure Elucidation ◽  
Chemical Structure ◽  
Soluble Fraction ◽  
Elution Curve ◽  
Mass Region ◽  
Milled Wood Lignin ◽  
Cellulose Solvent ◽  
Lignin Fraction ◽  
Partial Degradation

Abstract The residual wood meal left after extraction of milled wood lignin (MWL) was extracted with lithium chloride/N,N-dimethylacetamide, which is a well-known cellulose solvent, to afford a soluble fraction (cellulose-lignin fraction; CL) in 36.7% yield. The UV elution curve of CL acetate has the same profile as its refractive index (RI) elution curve. After partial degradation of CL by cellulase, the UV elution curve of CL acetate shifted to the low-molecular-mass region in a similar fashion as its RI elution curve. These results indicate that the lignin in CL (CL lignin) is chemically bonded to cellulose. On the other hand, half of the CL lignin was removed by xylanase treatment. It was concluded that approximately half of the CL lignin existed as a lignin-cellulose-xylan complex.

Sign in / Sign up

Export Citation Format

Share Document