Methoxy and methylthio-substituted trans-stilbene derivatives as CYP1B1 inhibitors – QSAR study with detailed interpretation of molecular descriptors
A quantitative structure–activity relationship (QSAR) model was built using multiple linear regression (MLR) to predict the ability of series methyl and/or methylthio trans-stilbene derivatives to inhibit CYP1B1. Twenty-four compounds with their activity expressed as the negative log of the IC50 val...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Arabian Journal of Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535222005202 |
| _version_ | 1811337341288054784 |
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| author | Natalia Piekuś-Słomka Mariusz Zapadka Bogumiła Kupcewicz |
| author_facet | Natalia Piekuś-Słomka Mariusz Zapadka Bogumiła Kupcewicz |
| author_sort | Natalia Piekuś-Słomka |
| collection | DOAJ |
| description | A quantitative structure–activity relationship (QSAR) model was built using multiple linear regression (MLR) to predict the ability of series methyl and/or methylthio trans-stilbene derivatives to inhibit CYP1B1. Twenty-four compounds with their activity expressed as the negative log of the IC50 value (pIC50 [M]) were split into a training (20 compounds) and a test set (four compounds) using Kennard and Stone algorithm. Molecular descriptors were calculated using alvaDesc software after compound optimization in the Gaussian 09 package in PL-Grid. The model characterized by the best validation parameters (R2TRAIN = 0.954, Q2LOO = 0.898, R2TEST = 0.880) was chosen based on the chemometric method – cluster analysis. The applicability domain has been determined, indicating that the regression model can give reliable prediction. The study shows that the inhibitory activity against CYP1B1 of the methyl and/or methylthio trans-stilbene derivatives can be predicted by RDF035m, Mor10m, Eig04_AEA(bo), RDF070s, MaxDD descriptors. Finally, the paper attempts to interpret three-dimensional descriptors by assessing the impact of interatomic interactions, following the partition of molecules into fragments, on the final value of descriptors. |
| first_indexed | 2024-04-13T17:53:27Z |
| format | Article |
| id | doaj.art-a9b5d302baa74da9a232b9f58afaf9c2 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-04-13T17:53:27Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-a9b5d302baa74da9a232b9f58afaf9c22022-12-22T02:36:36ZengElsevierArabian Journal of Chemistry1878-53522022-11-011511104204Methoxy and methylthio-substituted trans-stilbene derivatives as CYP1B1 inhibitors – QSAR study with detailed interpretation of molecular descriptorsNatalia Piekuś-Słomka0Mariusz Zapadka1Bogumiła Kupcewicz2Corresponding author.; Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Jurasza 2, 85-089 Bydgoszcz, PolandDepartment of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Jurasza 2, 85-089 Bydgoszcz, PolandDepartment of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Jurasza 2, 85-089 Bydgoszcz, PolandA quantitative structure–activity relationship (QSAR) model was built using multiple linear regression (MLR) to predict the ability of series methyl and/or methylthio trans-stilbene derivatives to inhibit CYP1B1. Twenty-four compounds with their activity expressed as the negative log of the IC50 value (pIC50 [M]) were split into a training (20 compounds) and a test set (four compounds) using Kennard and Stone algorithm. Molecular descriptors were calculated using alvaDesc software after compound optimization in the Gaussian 09 package in PL-Grid. The model characterized by the best validation parameters (R2TRAIN = 0.954, Q2LOO = 0.898, R2TEST = 0.880) was chosen based on the chemometric method – cluster analysis. The applicability domain has been determined, indicating that the regression model can give reliable prediction. The study shows that the inhibitory activity against CYP1B1 of the methyl and/or methylthio trans-stilbene derivatives can be predicted by RDF035m, Mor10m, Eig04_AEA(bo), RDF070s, MaxDD descriptors. Finally, the paper attempts to interpret three-dimensional descriptors by assessing the impact of interatomic interactions, following the partition of molecules into fragments, on the final value of descriptors.http://www.sciencedirect.com/science/article/pii/S1878535222005202Trans-stilbeneCYP1B1 inhibitionQSARMolecular descriptors |
| spellingShingle | Natalia Piekuś-Słomka Mariusz Zapadka Bogumiła Kupcewicz Methoxy and methylthio-substituted trans-stilbene derivatives as CYP1B1 inhibitors – QSAR study with detailed interpretation of molecular descriptors Arabian Journal of Chemistry Trans-stilbene CYP1B1 inhibition QSAR Molecular descriptors |
| title | Methoxy and methylthio-substituted trans-stilbene derivatives as CYP1B1 inhibitors – QSAR study with detailed interpretation of molecular descriptors |
| title_full | Methoxy and methylthio-substituted trans-stilbene derivatives as CYP1B1 inhibitors – QSAR study with detailed interpretation of molecular descriptors |
| title_fullStr | Methoxy and methylthio-substituted trans-stilbene derivatives as CYP1B1 inhibitors – QSAR study with detailed interpretation of molecular descriptors |
| title_full_unstemmed | Methoxy and methylthio-substituted trans-stilbene derivatives as CYP1B1 inhibitors – QSAR study with detailed interpretation of molecular descriptors |
| title_short | Methoxy and methylthio-substituted trans-stilbene derivatives as CYP1B1 inhibitors – QSAR study with detailed interpretation of molecular descriptors |
| title_sort | methoxy and methylthio substituted trans stilbene derivatives as cyp1b1 inhibitors qsar study with detailed interpretation of molecular descriptors |
| topic | Trans-stilbene CYP1B1 inhibition QSAR Molecular descriptors |
| url | http://www.sciencedirect.com/science/article/pii/S1878535222005202 |
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