Prediction of pEC50(M) and molecular docking study for the selective inhibition of arachidonate 5-lipoxygenase
Arachidonate 5-lipoxygenase (ALOX5) is considered a prime target for drug discovery in the area of liver fibrosis, rheumatoid arthritis, atherosclerosis, cancer and asthma. To date, the lead rate in the discovery of drugs that inhibit ALOX5 for the treatment of the above diseases is not satisfactory...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry
2021-12-01
|
| Series: | The Ukrainian Biochemical Journal |
| Subjects: | |
| Online Access: | http://ukrbiochemjournal.org/wp-content/uploads/2021/12/Das_6_21.pdf |
| _version_ | 1797668863456837632 |
|---|---|
| author | N. R. Das P. G. R. Achary |
| author_facet | N. R. Das P. G. R. Achary |
| author_sort | N. R. Das |
| collection | DOAJ |
| description | Arachidonate 5-lipoxygenase (ALOX5) is considered a prime target for drug discovery in the area of liver fibrosis, rheumatoid arthritis, atherosclerosis, cancer and asthma. To date, the lead rate in the discovery of drugs that inhibit ALOX5 for the treatment of the above diseases is not satisfactory. So, the development of powerful and effective ALOX5-targeted drugs is desired. In this regard, Quantitative Structure-Activity Relationship (QSAR) and molecular docking can have a major role in screening and designing drugs. In this work, 3D-QSAR models were proposed, which were built using the techniques like Multiple Linear Regression (MLR), and Partial Least Squares (PLS) for the pEC50(M) taking a diverse dataset of 112 molecules. The technique of the ‘Index of Ideality of Correlation (IIC)’ was also investigated to generate an optimal descriptor derived from the SMILES molecular structure. The effect of the number and nature of descriptors on the model were analyzed. The models can be helpful in providing better directions for the development of novel drug targets for 5-lipoxygenase. A significant improvement in the stability of the model was observed by the incorporation of the optimal descriptor. The molecular docking results showed that the ALOX5 receptor was well inhibited by the 112 ligands showing the least binding energy (-10.8 Kcal/mol). In order to validate the binding mode of the ligands docked with AutoDock Vina software, the top-scored compounds were re-docked using DockThor online docking server. The results obtained from docking suggest that the ligands with IDs 18, 20, 24, 30 and 44 are some of the potential inhibitors for ALOX5. |
| first_indexed | 2024-03-11T20:34:42Z |
| format | Article |
| id | doaj.art-d12012b1861e4d6b9f185cf6b3df8207 |
| institution | Directory Open Access Journal |
| issn | 2409-4943 2413-5003 |
| language | English |
| last_indexed | 2024-03-11T20:34:42Z |
| publishDate | 2021-12-01 |
| publisher | National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry |
| record_format | Article |
| series | The Ukrainian Biochemical Journal |
| spelling | doaj.art-d12012b1861e4d6b9f185cf6b3df82072023-10-02T07:19:13ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryThe Ukrainian Biochemical Journal2409-49432413-50032021-12-0193610111810.15407/ubj93.06.101Prediction of pEC50(M) and molecular docking study for the selective inhibition of arachidonate 5-lipoxygenaseN. R. Das0https://orcid.org/0000-0003-4153-8504P. G. R. Achary1https://orcid.org/0000-0002-9631-3356Department of CSIT, Siksha ‘O’ Anusandhan deemed to be University, Bhubaneswar, Odisha, IndiaDepartment of Chemistry, Faculty of Engineering and Technology (ITER), Siksha ‘O’ Anusandhan deemed to be University, Bhubaneswar, Odisha, IndiaArachidonate 5-lipoxygenase (ALOX5) is considered a prime target for drug discovery in the area of liver fibrosis, rheumatoid arthritis, atherosclerosis, cancer and asthma. To date, the lead rate in the discovery of drugs that inhibit ALOX5 for the treatment of the above diseases is not satisfactory. So, the development of powerful and effective ALOX5-targeted drugs is desired. In this regard, Quantitative Structure-Activity Relationship (QSAR) and molecular docking can have a major role in screening and designing drugs. In this work, 3D-QSAR models were proposed, which were built using the techniques like Multiple Linear Regression (MLR), and Partial Least Squares (PLS) for the pEC50(M) taking a diverse dataset of 112 molecules. The technique of the ‘Index of Ideality of Correlation (IIC)’ was also investigated to generate an optimal descriptor derived from the SMILES molecular structure. The effect of the number and nature of descriptors on the model were analyzed. The models can be helpful in providing better directions for the development of novel drug targets for 5-lipoxygenase. A significant improvement in the stability of the model was observed by the incorporation of the optimal descriptor. The molecular docking results showed that the ALOX5 receptor was well inhibited by the 112 ligands showing the least binding energy (-10.8 Kcal/mol). In order to validate the binding mode of the ligands docked with AutoDock Vina software, the top-scored compounds were re-docked using DockThor online docking server. The results obtained from docking suggest that the ligands with IDs 18, 20, 24, 30 and 44 are some of the potential inhibitors for ALOX5.http://ukrbiochemjournal.org/wp-content/uploads/2021/12/Das_6_21.pdf5-lipoxygenasemolecular dockingqsarsmiles |
| spellingShingle | N. R. Das P. G. R. Achary Prediction of pEC50(M) and molecular docking study for the selective inhibition of arachidonate 5-lipoxygenase The Ukrainian Biochemical Journal 5-lipoxygenase molecular docking qsar smiles |
| title | Prediction of pEC50(M) and molecular docking study for the selective inhibition of arachidonate 5-lipoxygenase |
| title_full | Prediction of pEC50(M) and molecular docking study for the selective inhibition of arachidonate 5-lipoxygenase |
| title_fullStr | Prediction of pEC50(M) and molecular docking study for the selective inhibition of arachidonate 5-lipoxygenase |
| title_full_unstemmed | Prediction of pEC50(M) and molecular docking study for the selective inhibition of arachidonate 5-lipoxygenase |
| title_short | Prediction of pEC50(M) and molecular docking study for the selective inhibition of arachidonate 5-lipoxygenase |
| title_sort | prediction of pec50 m and molecular docking study for the selective inhibition of arachidonate 5 lipoxygenase |
| topic | 5-lipoxygenase molecular docking qsar smiles |
| url | http://ukrbiochemjournal.org/wp-content/uploads/2021/12/Das_6_21.pdf |
| work_keys_str_mv | AT nrdas predictionofpec50mandmoleculardockingstudyfortheselectiveinhibitionofarachidonate5lipoxygenase AT pgrachary predictionofpec50mandmoleculardockingstudyfortheselectiveinhibitionofarachidonate5lipoxygenase |