scholarly journals Characterization of Drug-like Chemical Space for Cytotoxic Marine Metabolites Using Multivariate Methods

ACS Omega ◽  
2019 ◽  
Vol 4 (3) ◽  
pp. 5402-5411 ◽  
Author(s):  
Ramesh Jagannathan
Keyword(s):  
Chemical Space ◽  
Multivariate Methods ◽  
Marine Metabolites

scholarly journals BIOFACQUIM: A Mexican Compound Database of Natural Products

Biomolecules ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 31 ◽  
Author(s):  
B. Pilón-Jiménez ◽  
Fernanda Saldívar-González ◽  
Bárbara Díaz-Eufracio ◽  
José Medina-Franco
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Physicochemical Properties ◽  
Chemical Space ◽  
Structural Diversity ◽  
Proof Of Concept ◽  
Molecular Fingerprints ◽  
The Public ◽  
Compound Database

Compound databases of natural products have a major impact on drug discovery projects and other areas of research. The number of databases in the public domain with compounds with natural origins is increasing. Several countries, Brazil, France, Panama and, recently, Vietnam, have initiatives in place to construct and maintain compound databases that are representative of their diversity. In this proof-of-concept study, we discuss the first version of BIOFACQUIM, a novel compound database with natural products isolated and characterized in Mexico. We discuss its construction, curation, and a complete chemoinformatic characterization of the content and coverage in chemical space. The profile of physicochemical properties, scaffold content, and diversity, as well as structural diversity based on molecular fingerprints is reported. BIOFACQUIM is available for free.

scholarly journals Identification and characterization of an atypical Gαs-biased β2AR agonist that fails to evoke airway smooth muscle cell tachyphylaxis

2021 ◽  
Vol 118 (49) ◽  
pp. e2026668118
Author(s):  
Donghwa Kim ◽  
Alina Tokmakova ◽  
Lauren K. Lujan ◽  
Hannah R. Strzelinski ◽  
Nicholas Kim ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Chemical Space ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Airway Smooth Muscle Cell ◽  
Functional Studies ◽  
G Protein Coupled ◽  
Identification And Characterization

G protein–coupled receptors display multifunctional signaling, offering the potential for agonist structures to promote conformational selectivity for biased outputs. For β2-adrenergic receptors (β2AR), unbiased agonists stabilize conformation(s) that evoke coupling to Gαs (cyclic adenosine monophosphate [cAMP] production/human airway smooth muscle [HASM] cell relaxation) and β-arrestin engagement, the latter acting to quench Gαs signaling, contributing to receptor desensitization/tachyphylaxis. We screened a 40-million-compound scaffold ranking library, revealing unanticipated agonists with dihydroimidazolyl-butyl-cyclic urea scaffolds. The S-stereoisomer of compound C1 shows no detectable β-arrestin engagement/signaling by four methods. However, C1-S retained Gαs signaling—a divergence of the outputs favorable for treating asthma. Functional studies with two models confirmed the biasing: β2AR-mediated cAMP signaling underwent desensitization to the unbiased agonist albuterol but not to C1-S, and desensitization of HASM cell relaxation was observed with albuterol but not with C1-S. These HASM results indicate biologically pertinent biasing of C1-S, in the context of the relevant physiologic response, in the human cell type of interest. Thus, C1-S was apparently strongly biased away from β-arrestin, in contrast to albuterol and C5-S. C1-S structural modeling and simulations revealed binding differences compared with unbiased epinephrine at transmembrane (TM) segments 3,5,6,7 and ECL2. C1-S (R2 = cyclohexane) was repositioned in the pocket such that it lost a TM6 interaction and gained a TM7 interaction compared with the analogous unbiased C5-S (R2 = benzene group), which appears to contribute to C1-S biasing away from β-arrestin. Thus, an agnostic large chemical-space library identified agonists with receptor interactions that resulted in relevant signal splitting of β2AR actions favorable for treating obstructive lung disease.

Near-Infrared Spectroscopy Coupled with Multivariate Methods for the Characterization of Ethanol Adulteration in Premium 91 Gasoline

2017 ◽  
Vol 31 (7) ◽  
pp. 7591-7597 ◽  
Author(s):  
Fazal Mabood ◽  
Ricard Boqué ◽  
Ahmad Hamaed ◽  
Farah Jabeen ◽  
Ahmed Al-Harrasi ◽  
...  
Keyword(s):  
Infrared Spectroscopy ◽  
Near Infrared Spectroscopy ◽  
Near Infrared ◽  
Multivariate Methods

Epigenetic relevant chemical space: a chemoinformatic characterization of inhibitors of DNA methyltransferases

RSC Advances ◽  
2015 ◽  
Vol 5 (106) ◽  
pp. 87465-87476 ◽  
Author(s):  
Eli Fernández-de Gortari ◽  
José L. Medina-Franco
Keyword(s):  
Chemical Space ◽  
Dna Methyltransferases

The first comprehensive exploration of the epigenetic relevant chemical space is reported in this work with a special emphasis on inhibitors of DNA methyltransferases.

Characterization of wild‐type and mutant p53 protein by Raman spectroscopy and multivariate methods

2019 ◽  
Vol 50 (10) ◽  
pp. 1388-1394 ◽  
Author(s):  
Karen Hernández‐Vidales ◽  
Edgar Guevara ◽  
Vanesa Olivares‐Illana ◽  
Francisco Javier González
Keyword(s):  
Raman Spectroscopy ◽  
P53 Protein ◽  
Mutant P53 ◽  
Multivariate Methods ◽  
Wild Type

Sensory Evaluation of Walnut: An Interlaboratory Study

2001 ◽  
Vol 7 (1) ◽  
pp. 37-47 ◽  
Author(s):  
F. Sinesio ◽  
L. Guerrero ◽  
A. Romero ◽  
E. Moneta ◽  
J. C. Lombard
Keyword(s):  
Sensory Quality ◽  
Sensory Information ◽  
Procrustes Analysis ◽  
Interlaboratory Study ◽  
Multivariate Methods ◽  
Generalized Procrustes Analysis ◽  
Product Classification ◽  
Similar Product

This work summarizes an interlaboratory study on full sensory profiling designed with the aim of finding some key attributes relevant to describe the sensory quality of walnuts. The study compared descriptive sensory profiling by different laboratories in different countries (Spain, France and Italy) Three trained panels in those European countries in the characterization of walnuts were used. Samples of walnuts belonging to different cultivars were harvested from experimental fields and some commercial lots. Multivariate methods (generalized procrustes analysis and varclus procedure) of analysis were used for extracting useful sensory information about the products and the variability between the panels. The descriptive profiles generated by the panels independently showed some analogies and provided similar product classification.

scholarly journals Comprehensive machine learning based study of the chemical space of herbicides

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Davor Oršolić ◽  
Vesna Pehar ◽  
Tomislav Šmuc ◽  
Višnja Stepanić
Keyword(s):  
Natural Products ◽  
Predictive Models ◽  
Chemical Space ◽  
Data Set ◽  
Modes Of Action ◽  
Molecular Features ◽  
Global Increase ◽  
Screening Platform ◽  
Weed Resistance

AbstractWidespread use of herbicides results in the global increase in weed resistance. The rotational use of herbicides according to their modes of action (MoAs) and discovery of novel phytotoxic molecules are the two strategies used against the weed resistance. Herein, Random Forest modeling was used to build predictive models and establish comprehensive characterization of structure–activity relationships underlying herbicide classifications according to their MoAs and weed selectivity. By combining the predictive models with herbicide-likeness rules defined by selected molecular features (numbers of H-bond acceptors and donors, logP, topological and relative polar surface area, and net charge), the virtual stepwise screening platform is proposed for characterization of small weight molecules for their phytotoxic properties. The screening cascade was applied on the data set of phytotoxic natural products. The obtained results may be valuable for refinement of herbicide rotational program as well as for discovery of novel herbicides primarily among natural products as a source for molecules of novel structures and novel modes of action and translocation profiles as compared with the synthetic compounds.

scholarly journals Structuring Chemical Space: Similarity-Based Characterization of the PubChem Database

2010 ◽  
Vol 29 (1-2) ◽  
pp. 37-49 ◽  
Author(s):  
Giovanni Cincilla ◽  
Michael Thormann ◽  
Miquel Pons
Keyword(s):  
Chemical Space ◽  
Pubchem Database
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