Atom-based Stochastic and non-Stochastic 3D-Chiral Bilinear Indices and their Applications to Central Chirality Codification

Castillo-Garit, Juan A.; Marrero-Ponce, Yovani; Torrens, Francisco; Rotondo, Richard

doi:10.3390/ecsoc-10-01448

Cited by 5 publications

(9 citation statements)

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“…Permeability data for a set of 28 compounds in Calu-3 cells were collated from the literature. [29][30][31][32][33] Permeability in Calu-3 cells was also correlated to the in vitro permeability for the same set of compounds in Caco-2 cells, 25,34 so that Caco-2 permeability can be used to predict Calu-3 permeability. A QSAR model to predict in vitro Calu-3 permeability using physicochemical properties was also developed.…”

Section: Passive Permeability Estimatesmentioning

confidence: 99%

Development of a Multicompartment Permeability‐Limited Lung PBPK Model and Its Application in Predicting Pulmonary Pharmacokinetics of Antituberculosis Drugs

Gaohua

Wedagedera

Small

et al. 2015

CPT Pharmacom & Syst Pharma

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Achieving sufficient concentrations of antituberculosis (TB) drugs in pulmonary tissue at the optimum time is still a challenge in developing therapeutic regimens for TB. A physiologically based pharmacokinetic model incorporating a multicompartment permeability-limited lung model was developed and used to simulate plasma and pulmonary concentrations of seven drugs. Passive permeability of drugs within the lung was predicted using an in vitro-in vivo extrapolation approach. Simulated epithelial lining fluid (ELF):plasma concentration ratios showed reasonable agreement with observed clinical data for rifampicin, isoniazid, ethambutol, and erythromycin. For clarithromycin, itraconazole and pyrazinamide the observed ELF:plasma ratios were significantly underpredicted. Sensitivity analyses showed that changing ELF pH or introducing efflux transporter activity between lung tissue and ELF can alter the ELF:plasma concentration ratios. The described model has shown utility in predicting the lung pharmacokinetics of anti-TB drugs and provides a framework for predicting pulmonary concentrations of novel anti-TB drugs.

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Section: Passive Permeability Estimatesmentioning

confidence: 99%

Development of a Multicompartment Permeability‐Limited Lung PBPK Model and Its Application in Predicting Pulmonary Pharmacokinetics of Antituberculosis Drugs

Gaohua

Wedagedera

Small

et al. 2015

CPT Pharmacom & Syst Pharma

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“…2). At iteration 3, the neighborhood in G of these oxygen atoms are added to H 3 C , hence adding N and Br which allow to differentiate both paths and thus removes the equivalent ordered isomorphism f from F 3 C .…”

Section: Minimal Stereo Subgraphmentioning

confidence: 99%

Incorporating Molecule’s Stereisomerism within the Machine Learning Framework

Grenier

Brun

Villemin

2014

Lecture Notes in Computer Science

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An important field of chemoinformatics consists in the prediction of molecule's properties, and within this field, graph kernels constitute a powerful framework thanks to their ability to combine a natural encoding of molecules by graphs, with classical statistical tools. Unfortunately some molecules encoded by a same graph and differing only by the three dimensional orientation of their atoms in space have different properties. Such molecules are called stereoisomers. These latter properties can not be predicted by usual graph methods which do not encode stereoisomerism. In this paper we propose to encode the stereoisomerism property of each atom of a molecule by a local subgraph. A kernel between bags of such subgraphs provides a similarity measure incorporating stereoisomerism properties. We then propose two extensions of this kernel incorporating in each sub graph information about its surroundings.

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“…The theory of the atom-based bilinear indices used in this study was discussed in detail in earlier publications (31,32). Specifically, the CARDD (Computed-Aided Rational Drug Design) module implemented in the TOMOCOMD Software ( a ) was used in the calculation of atom-based non-stochastic and stochastic bilinear indices.…”

Section: Computational Approachmentioning

confidence: 99%

“…In fact, this scheme has been successfully applied to the prediction of several physical, physicochemical, chemical, pharmacokinetical, toxicological as well as biological properties (20)(21)(22)(23)(24)(25). Furthermore, these molecular descriptors (MDs) have been extended to consider three-dimensional (3D) features of small-⁄ medium-sized molecules based on the trigonometric-3D-chirality-correction factor approach (26)(27)(28)(29)(30)(31).…”

mentioning

confidence: 99%

Identification In Silico and In Vitro of Novel Trypanosomicidal Drug‐Like Compounds

et al. 2012

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Atom-based bilinear indices and linear discriminant analysis are used to discover novel trypanosomicidal compounds. The obtained linear discriminant analysis-based quantitative structure-activity relationship models, using non-stochastic and stochastic indices, provide accuracies of 89.02% (85.11%) and 89.60% (88.30%) of the chemicals in the training (test) sets, respectively. Later, both models were applied to the virtual screening of 18 in-house synthesized compounds to find new pro-lead antitrypanosomal agents. The in vitro antitrypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi is assayed. Predictions agree with experimental results to a great extent (16 ⁄ 18) of the chemicals. Sixteen compounds show more than 70% of epimastigote inhibition at a concentration 100 lg ⁄ mL. In addition, three compounds (CRIS 112, CRIS 140 and CRIS 147) present more than 70% of epimastigote inhibition at a concentration of 10 lg ⁄ mL (79.95%, 73.97% and 78.13%, respectively) with low values of cytotoxicity (19.7%, 7.44% and 20.63%, correspondingly).Taking into account all these results, we could say that these three compounds could be optimized in forthcoming works. Even though none of them resulted more active than nifurtimox, the current results constitute a step forward in the search for efficient ways to discover new lead antitrypanosomals.

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Atom-based Stochastic and non-Stochastic 3D-Chiral Bilinear Indices and their Applications to Central Chirality Codification

Cited by 5 publications

References 0 publications

Development of a Multicompartment Permeability‐Limited Lung PBPK Model and Its Application in Predicting Pulmonary Pharmacokinetics of Antituberculosis Drugs

Development of a Multicompartment Permeability‐Limited Lung PBPK Model and Its Application in Predicting Pulmonary Pharmacokinetics of Antituberculosis Drugs

Incorporating Molecule’s Stereisomerism within the Machine Learning Framework

Identification In Silico and In Vitro of Novel Trypanosomicidal Drug‐Like Compounds

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