Discrimination of Naturally-Occurring 2-Arylbenzofurans as Cyclooxygenase-2 Inhibitors: Insights into the Binding Mode and Enzymatic Inhibitory Activity
2-arylbenzofuran-containing compounds are chemical entities that can be naturally produced by several organisms. A wide-range of activities is described for several compounds of this kind and they are, therefore, valuable moieties for a lead finding from nature. Although there are in-vitro data abou...
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| Format: | Article |
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MDPI AG
2020-01-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/2/176 |
| _version_ | 1818946458524581888 |
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| author | Ericsson Coy-Barrera |
| author_facet | Ericsson Coy-Barrera |
| author_sort | Ericsson Coy-Barrera |
| collection | DOAJ |
| description | 2-arylbenzofuran-containing compounds are chemical entities that can be naturally produced by several organisms. A wide-range of activities is described for several compounds of this kind and they are, therefore, valuable moieties for a lead finding from nature. Although there are in-vitro data about the activity of 2-arylbenzofuran-related compounds against cyclooxygenase (COX) enzymes, the molecular level of these COX-inhibiting constituents had not been deeply explored. Thus, 58 2-arylbenzofurans were initially screened through molecular docking within the active site of nine COX-2 crystal structures. The resulting docking scores were statistically analyzed and good reproducibility and convergence were found to discriminate the best-docked compounds. Discriminated compounds exhibited the best performance in molecular dynamics simulations as well as the most-favorable binding energies and the lowest in-vitro IC<sub>50</sub> values for COX-2 inhibition. A three-dimensional quantitative activity-structure relationship (3D-QSAR) was also demonstrated, which showed some crucial structural requirements for enhanced enzyme inhibition. Therefore, four hits are proposed as lead structures for the development of COX-2 inhibitors based on 2-arylbenzofurans in further studies. |
| first_indexed | 2024-12-20T08:15:20Z |
| format | Article |
| id | doaj.art-03378adb498f49f59826c4135f639cba |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-20T08:15:20Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-03378adb498f49f59826c4135f639cba2022-12-21T19:47:09ZengMDPI AGBiomolecules2218-273X2020-01-0110217610.3390/biom10020176biom10020176Discrimination of Naturally-Occurring 2-Arylbenzofurans as Cyclooxygenase-2 Inhibitors: Insights into the Binding Mode and Enzymatic Inhibitory ActivityEricsson Coy-Barrera0Bioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Cajicá 250247, Colombia2-arylbenzofuran-containing compounds are chemical entities that can be naturally produced by several organisms. A wide-range of activities is described for several compounds of this kind and they are, therefore, valuable moieties for a lead finding from nature. Although there are in-vitro data about the activity of 2-arylbenzofuran-related compounds against cyclooxygenase (COX) enzymes, the molecular level of these COX-inhibiting constituents had not been deeply explored. Thus, 58 2-arylbenzofurans were initially screened through molecular docking within the active site of nine COX-2 crystal structures. The resulting docking scores were statistically analyzed and good reproducibility and convergence were found to discriminate the best-docked compounds. Discriminated compounds exhibited the best performance in molecular dynamics simulations as well as the most-favorable binding energies and the lowest in-vitro IC<sub>50</sub> values for COX-2 inhibition. A three-dimensional quantitative activity-structure relationship (3D-QSAR) was also demonstrated, which showed some crucial structural requirements for enhanced enzyme inhibition. Therefore, four hits are proposed as lead structures for the development of COX-2 inhibitors based on 2-arylbenzofurans in further studies.https://www.mdpi.com/2218-273X/10/2/176cyclooxygenase-22-arylbenzofuransenzymatic activity |
| spellingShingle | Ericsson Coy-Barrera Discrimination of Naturally-Occurring 2-Arylbenzofurans as Cyclooxygenase-2 Inhibitors: Insights into the Binding Mode and Enzymatic Inhibitory Activity Biomolecules cyclooxygenase-2 2-arylbenzofurans enzymatic activity |
| title | Discrimination of Naturally-Occurring 2-Arylbenzofurans as Cyclooxygenase-2 Inhibitors: Insights into the Binding Mode and Enzymatic Inhibitory Activity |
| title_full | Discrimination of Naturally-Occurring 2-Arylbenzofurans as Cyclooxygenase-2 Inhibitors: Insights into the Binding Mode and Enzymatic Inhibitory Activity |
| title_fullStr | Discrimination of Naturally-Occurring 2-Arylbenzofurans as Cyclooxygenase-2 Inhibitors: Insights into the Binding Mode and Enzymatic Inhibitory Activity |
| title_full_unstemmed | Discrimination of Naturally-Occurring 2-Arylbenzofurans as Cyclooxygenase-2 Inhibitors: Insights into the Binding Mode and Enzymatic Inhibitory Activity |
| title_short | Discrimination of Naturally-Occurring 2-Arylbenzofurans as Cyclooxygenase-2 Inhibitors: Insights into the Binding Mode and Enzymatic Inhibitory Activity |
| title_sort | discrimination of naturally occurring 2 arylbenzofurans as cyclooxygenase 2 inhibitors insights into the binding mode and enzymatic inhibitory activity |
| topic | cyclooxygenase-2 2-arylbenzofurans enzymatic activity |
| url | https://www.mdpi.com/2218-273X/10/2/176 |
| work_keys_str_mv | AT ericssoncoybarrera discriminationofnaturallyoccurring2arylbenzofuransascyclooxygenase2inhibitorsinsightsintothebindingmodeandenzymaticinhibitoryactivity |