Development of improved QSAR models for predicting the outcome of the in vivo micronucleus genetic toxicity assay

2020 ◽  
Vol 113 ◽  
pp. 104620 ◽  
Author(s):  
Jae Wook Yoo ◽  
Naomi L. Kruhlak ◽  
Curran Landry ◽  
Kevin P. Cross ◽  
Alexander Sedykh ◽  
...  
Keyword(s):  
Toxicity Assay ◽  
Genetic Toxicity ◽  
Qsar Models

Evaluation of the in vivo genetic toxicity of concentrated barley β-glucan

2004 ◽  
Vol 42 (1) ◽  
pp. 155-156 ◽  
Author(s):  
Bryan Delaney ◽  
Nico de Vogel ◽  
Cyrille A.M Krul
Keyword(s):  
Genetic Toxicity

scholarly journals New Antitrichomonal Drug-like Chemicals Selected by Bond (Edge)-Based TOMOCOMD-CARDD Descriptors

2008 ◽  
Vol 13 (8) ◽  
pp. 785-794 ◽  
Author(s):  
Alfredo Meneses-Marcel ◽  
Oscar M. Rivera-Borroto ◽  
Yovani Marrero-Ponce ◽  
Alina Montero ◽  
Yanetsy Machado Tugores ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Molecular Descriptors ◽  
Correlation Coefficients ◽  
Linear Discriminant ◽  
Structure Activity ◽  
Qsar Models ◽  
Test Sets ◽  
Quantitative Structure Activity Relationships ◽  
Edge Based

Bond-based quadratic indices, new TOMOCOMD-CARDD molecular descriptors, and linear discriminant analysis (LDA) were used to discover novel lead trichomonacidals. The obtained LDA-based quantitative structure-activity relationships (QSAR) models, using nonstochastic and stochastic indices, were able to classify correctly 87.91% (87.50%) and 89.01% (84.38%) of the chemicals in training (test) sets, respectively. They showed large Matthews correlation coefficients of 0.75 (0.71) and 0.78 (0.65) for the training (test) sets, correspondingly. Later, both models were applied to the virtual screening of 21 chemicals to find new lead antitrichomonal agents. Predictions agreed with experimental results to a great extent because a correct classification for both models of 95.24% (20 of 21) of the chemicals was obtained. Of the 21 compounds that were screened and synthesized, 2 molecules (chemicals G-1, UC-245) showed high to moderate cytocidal activity at the concentration of 10 μg/ml, another 2 compounds (G-0 and CRIS-148) showed high cytocidal activity only at the concentration of 100 μg/ml, and the remaining chemicals (from CRIS-105 to CRIS-153, except CRIS-148) were inactive at these assayed concentrations. Finally, the best candidate, G-1 (cytocidal activity of 100% at 10 μg/ml) was in vivo assayed in ovariectomized Wistar rats achieving promising results as a trichomonacidal drug-like compound. (Journal of Biomolecular Screening 2008:785-794).

scholarly journals Results of in vitro and in vivo genetic toxicity tests on methyl isocyanate

1987 ◽  
Vol 72 ◽  
pp. 183-187 ◽  
Author(s):  
Michael D. Shelby ◽  
James W. Allen ◽  
William J. Caspary ◽  
Steven Haworth ◽  
James Ivett ◽  
...  
Keyword(s):  
Toxicity Tests ◽  
Methyl Isocyanate ◽  
Genetic Toxicity

Genetic Toxicity Studies of the Ketogenic Ester Bis Hexanoyl (R)-1,3-Butanediol

2021 ◽  
pp. 109158182199177
Author(s):  
Brianna J. Stubbs ◽  
Andrey I. Nikiforov ◽  
Marisa O. Rihner ◽  
Sari Weston ◽  
Nancy Higley ◽  
...  
Keyword(s):  
Micronucleus Test ◽  
Mutagenic Activity ◽  
Metabolic Activation ◽  
Coli Strain ◽  
Control Group ◽  
Sprague Dawley ◽  
Genetic Toxicity ◽  
Polychromatic Erythrocytes

A series of studies was conducted to assess the genetic toxicity of a novel ketone ester, bis hexanoyl (R)-1,3-butanediol (herein referred to as BH-BD), according to Organization for Economic Co-operation and Development testing guidelines under the standards of Good Laboratory Practices. In bacterial reverse mutation tests, there was no evidence of mutagenic activity in any of the Salmonella typhimurium strains tested or in Escherichia coli strain WP2 uvrA, at dose levels up to 5,000 μg/plate in the presence or absence of Aroclor 1254-induced rat liver (S9 mix) for metabolic activation. In the in vitro micronucleus test using human TK6 cells, BH-BD did not show a statistically significant increase in the number of cells containing micronuclei when compared with concurrent control cultures at all time points and at any of the concentrations analyzed (up to 100 μg/mL, final concentration in culture medium), with and without S9 mix activation. In the in vivo micronucleus test using Sprague Dawley rats, BH-BD did not show a statistically significant increase in the incidence of micronucleated polychromatic erythrocytes relative to the vehicle control group. Therefore, BH-BD was concluded to be negative in all 3 tests. These results support the safety assessment of BH-BD for potential use in food.

scholarly journals QSAR-ANALYSIS OF POLYSUBSTITUTED FUNCTIONALIZED AMINOTHIAZOLES WITH ANTIHYPERTENSIVE ACTIVITY

2020 ◽  
Vol 5 (2) ◽  
pp. 98-104
Author(s):  
I. V. Drapak
Keyword(s):  
Theoretical Basis ◽  
Molecular Descriptors ◽  
De Novo ◽  
Antihypertensive Drugs ◽  
Biologically Active ◽  
Antihypertensive Activity ◽  
Activity Parameter ◽  
Qsar Analysis ◽  
Qsar Models

Background. QSAR analysis is an important tool for the identification of pharmacophore fragments in biologically active substances and helps optimize the search for new effective drugs. Objective. The aim of the study was to determine the molecular descriptors for QSAR analysis of polysubstituted functionalized aminothiazoles as a theoretical basis for purposeful search de novo of potential antihypertensive drugs among the investigated compounds. Methods. Calculation of molecular descriptors and QSAR-models creation was carried out using the Hyper-Chem 7.5 and BuildQSAR packages. Results. The calculation of a number of molecular descriptors (electronic, steric, geometric, energy) was performed for 15 new polysubstituted functionalized aminothiazoles, with established in vivo antihypertensive activity. According to the calculated molecular descriptors and antihypertensive activity parameter, the QSAR models were derived НА = a + b ∙ X1 + c ∙ X2 + d ∙ X3 , where the activity parameter НА is antihypertensive activity and X1, X2, X3 are molecular descriptors. Conclusion. The study of ‘the structure - antihypertensive activity’ relationship for polysubstituted functionalized aminothiazoles was carried out. QSAR analysis revealed that volume, area, lipophilicity, dipole moment, refractivity, polarization of the molecule and energy of the lowest unoccupied molecular orbital have the most significant effect on antihypertensive activity. It was suggested that the attained QSAR-models may have antihypertensive activity within abovementioned row of compounds and can be considered as theoretical basis for de novo design of new potential antihypertensive drugs.

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