Application of Docking Analysis in the Prediction and Biological Evaluation of the Lipoxygenase Inhibitory Action of Thiazolyl Derivatives of Mycophenolic Acid
5-LOX inhibition is among the desired characteristics of anti-inflammatory drugs, while 15-LOX has also been considered as a drug target. Similarity in inhibition behavior between soybean LOX-1 and human 5-LOX has been observed and soybean LOX (sLOX) type 1b has been used for the evaluation of LOX i...
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MDPI AG
2018-07-01
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| Series: | Molecules |
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| author | Evangelia Tsolaki Phaedra Eleftheriou Victor Kartsev Athina Geronikaki Anil K. Saxena |
| author_facet | Evangelia Tsolaki Phaedra Eleftheriou Victor Kartsev Athina Geronikaki Anil K. Saxena |
| author_sort | Evangelia Tsolaki |
| collection | DOAJ |
| description | 5-LOX inhibition is among the desired characteristics of anti-inflammatory drugs, while 15-LOX has also been considered as a drug target. Similarity in inhibition behavior between soybean LOX-1 and human 5-LOX has been observed and soybean LOX (sLOX) type 1b has been used for the evaluation of LOX inhibition in drug screening for years. After prediction of LOX inhibition by PASS and docking as well as toxicity by PROTOX and ToxPredict sixteen (E)-N-(thiazol-2-yl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enamide derivatives with lengths varying from about 15–20 Å were evaluated in vitro for LOX inhibitory action using the soybean lipoxygenase sLOX 1b. Docking analysis was performed using soybean LOX L-1 (1YGE), soybean LOX-3 (1JNQ), human 5-LOX (3O8Y and 3V99) and mammalian 15-LOX (1LOX) structures. Different dimensions of target center and docking boxes and a cavity prediction algorithm were used. The compounds exhibited inhibitory action between 2.5 μΜ and 165 μΜ. Substituents with an electronegative atom at two-bond proximity to position 4 of the thiazole led to enhanced activity. Docking results indicated that the LOX structures 1JNQ, 3V99 and 1LOX can effectively be used for estimation of LOX inhibition and amino acid interactions of these compounds. |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-12T01:41:36Z |
| publishDate | 2018-07-01 |
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| series | Molecules |
| spelling | doaj.art-ef1700bfdda042d1bc23adcf5cac57442022-12-22T00:42:42ZengMDPI AGMolecules1420-30492018-07-01237162110.3390/molecules23071621molecules23071621Application of Docking Analysis in the Prediction and Biological Evaluation of the Lipoxygenase Inhibitory Action of Thiazolyl Derivatives of Mycophenolic AcidEvangelia Tsolaki0Phaedra Eleftheriou1Victor Kartsev2Athina Geronikaki3Anil K. Saxena4Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Medical Laboratories, School of Health and Care Professions, Alexander Technological Educational Institute of Thessaloniki, 54700 Thessaloniki, GreeceInterBioscreen, 119019 Moscow, RussiaDepartment of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDivision of Medicinal & Process Chemistry, Central Drug Research Institute, 226031 Lucknow, India5-LOX inhibition is among the desired characteristics of anti-inflammatory drugs, while 15-LOX has also been considered as a drug target. Similarity in inhibition behavior between soybean LOX-1 and human 5-LOX has been observed and soybean LOX (sLOX) type 1b has been used for the evaluation of LOX inhibition in drug screening for years. After prediction of LOX inhibition by PASS and docking as well as toxicity by PROTOX and ToxPredict sixteen (E)-N-(thiazol-2-yl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enamide derivatives with lengths varying from about 15–20 Å were evaluated in vitro for LOX inhibitory action using the soybean lipoxygenase sLOX 1b. Docking analysis was performed using soybean LOX L-1 (1YGE), soybean LOX-3 (1JNQ), human 5-LOX (3O8Y and 3V99) and mammalian 15-LOX (1LOX) structures. Different dimensions of target center and docking boxes and a cavity prediction algorithm were used. The compounds exhibited inhibitory action between 2.5 μΜ and 165 μΜ. Substituents with an electronegative atom at two-bond proximity to position 4 of the thiazole led to enhanced activity. Docking results indicated that the LOX structures 1JNQ, 3V99 and 1LOX can effectively be used for estimation of LOX inhibition and amino acid interactions of these compounds.http://www.mdpi.com/1420-3049/23/7/1621pharmacophoredockingLOXanti-inflammatorythiazoles |
| spellingShingle | Evangelia Tsolaki Phaedra Eleftheriou Victor Kartsev Athina Geronikaki Anil K. Saxena Application of Docking Analysis in the Prediction and Biological Evaluation of the Lipoxygenase Inhibitory Action of Thiazolyl Derivatives of Mycophenolic Acid Molecules pharmacophore docking LOX anti-inflammatory thiazoles |
| title | Application of Docking Analysis in the Prediction and Biological Evaluation of the Lipoxygenase Inhibitory Action of Thiazolyl Derivatives of Mycophenolic Acid |
| title_full | Application of Docking Analysis in the Prediction and Biological Evaluation of the Lipoxygenase Inhibitory Action of Thiazolyl Derivatives of Mycophenolic Acid |
| title_fullStr | Application of Docking Analysis in the Prediction and Biological Evaluation of the Lipoxygenase Inhibitory Action of Thiazolyl Derivatives of Mycophenolic Acid |
| title_full_unstemmed | Application of Docking Analysis in the Prediction and Biological Evaluation of the Lipoxygenase Inhibitory Action of Thiazolyl Derivatives of Mycophenolic Acid |
| title_short | Application of Docking Analysis in the Prediction and Biological Evaluation of the Lipoxygenase Inhibitory Action of Thiazolyl Derivatives of Mycophenolic Acid |
| title_sort | application of docking analysis in the prediction and biological evaluation of the lipoxygenase inhibitory action of thiazolyl derivatives of mycophenolic acid |
| topic | pharmacophore docking LOX anti-inflammatory thiazoles |
| url | http://www.mdpi.com/1420-3049/23/7/1621 |
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