Natural Phosphodiesterase-4 Inhibitors with Potential <i>Anti</i>-Inflammatory Activities from <i>Millettia dielsiana</i>
The results of in silico screening of the 50 isolated compounds from <i>Millettia dielsiana</i> against the target proteins PDE4 (PDE4A, PDE4B, and PDE4D) showed binding affinity ranges from −5.81 to −11.56, −5.27 to −13.01, and −5.80 to −12.12 kcal mol<sup>−1</sup>, respecti...
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| Format: | Article |
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MDPI AG
2023-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/21/7253 |
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| author | Vu Thi Thu Le Hoang Van Hung Nguyen Xuan Ha Cao Hong Le Pham Thi Hong Minh Do Tien Lam |
| author_facet | Vu Thi Thu Le Hoang Van Hung Nguyen Xuan Ha Cao Hong Le Pham Thi Hong Minh Do Tien Lam |
| author_sort | Vu Thi Thu Le |
| collection | DOAJ |
| description | The results of in silico screening of the 50 isolated compounds from <i>Millettia dielsiana</i> against the target proteins PDE4 (PDE4A, PDE4B, and PDE4D) showed binding affinity ranges from −5.81 to −11.56, −5.27 to −13.01, and −5.80 to −12.12 kcal mol<sup>−1</sup>, respectively, with median values of −8.83, −8.84, and −8.645 kcal mol<sup>−1</sup>, respectively. Among these compounds, Millesianin F was identified as the most promising PDE4A inhibitor due to its strongest binding affinity with the target protein PDE4A. (−11.56 kcal mol<sup>−1</sup>). This was followed by the compound 5,7,4′-trihydroxyisoflavone 7-<i>O-β</i>-<span style="font-variant: small-caps;">d</span>-apiofuranosyl-(1→6)-β-<span style="font-variant: small-caps;">d</span>-glucopyranoside (D50) with the binding affinity value of −11.35 kcal mol<sup>−1</sup>. For the target protein PDE4B, compound D50 exhibited the strongest binding affinity value of −13.01 kcal mol<sup>−1</sup>, while showing poorer inhibition ability for PDE4D. The 100 ns MD simulation examination (radius of gyration, Solvent Accessible Surface Area (SASA), Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), and hydrogen bonding) was carried out to examine the overall stability and binding efficiency of the protein–ligand complex between compounds (Millesianin F, Millesianin G, Claclrastin-7-<i>O-β</i>-<span style="font-variant: small-caps;">d</span>-glucopyranoside, 7-hydroxy-4′,6 dimethoxyisoflavone-7-<i>O-β</i>-<span style="font-variant: small-caps;">d</span>-apiofuranosyl-(1→6)-<i>β</i>-<span style="font-variant: small-caps;">d</span>-glucopyranoside, 7-hydroxy-4′,8-dimethoxyisoflavone 7-<i>O-β</i>-<span style="font-variant: small-caps;">d</span>-apiofuranosyl-(1→6)-β-<span style="font-variant: small-caps;">d</span>-glucopyranoside, Odoratin-7-<i>O-β</i>-<span style="font-variant: small-caps;">d</span>-glucopyranoside, and 5,7,4′-trihydroxyisoflavone 7-<i>O-β</i>-<span style="font-variant: small-caps;">d</span>-apiofuranosyl-(1→6)-<i>β</i>-<span style="font-variant: small-caps;">d</span>-glucopyranoside) and PDE4 (A, B) subtype proteins. Compound D50 has shown strong <i>anti</i>-inflammatory activity, as evidenced by experimental results. It effectively inhibits PDE4B and PDE4D, with IC<sub>50</sub> values of 6.56 ± 0.7 µM and 11.74 ± 1.3 µM, respectively. Additionally, it reduces NO production, with an IC<sub>50</sub> value of 5.40 ± 0.9 µM. Based on these findings, it is promising and considered a potential novel <i>anti</i>-inflammatory drug for future development. |
| first_indexed | 2024-03-11T11:25:53Z |
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| id | doaj.art-faf309e568224716b58c9dd9ac95ff33 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T11:25:53Z |
| publishDate | 2023-10-01 |
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| series | Molecules |
| spelling | doaj.art-faf309e568224716b58c9dd9ac95ff332023-11-10T15:08:23ZengMDPI AGMolecules1420-30492023-10-012821725310.3390/molecules28217253Natural Phosphodiesterase-4 Inhibitors with Potential <i>Anti</i>-Inflammatory Activities from <i>Millettia dielsiana</i>Vu Thi Thu Le0Hoang Van Hung1Nguyen Xuan Ha2Cao Hong Le3Pham Thi Hong Minh4Do Tien Lam5Thai Nguyen University of Agriculture and Forestry, Quyet Thang, Thai Nguyen 24119, VietnamThai Nguyen University-Lao Cai Campus, Thai Nguyen University, Lao Cai City 31000, VietnamInstitute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi 10072, VietnamThai Nguyen University of Agriculture and Forestry, Quyet Thang, Thai Nguyen 24119, VietnamInstitute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi 10072, VietnamInstitute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi 10072, VietnamThe results of in silico screening of the 50 isolated compounds from <i>Millettia dielsiana</i> against the target proteins PDE4 (PDE4A, PDE4B, and PDE4D) showed binding affinity ranges from −5.81 to −11.56, −5.27 to −13.01, and −5.80 to −12.12 kcal mol<sup>−1</sup>, respectively, with median values of −8.83, −8.84, and −8.645 kcal mol<sup>−1</sup>, respectively. Among these compounds, Millesianin F was identified as the most promising PDE4A inhibitor due to its strongest binding affinity with the target protein PDE4A. (−11.56 kcal mol<sup>−1</sup>). This was followed by the compound 5,7,4′-trihydroxyisoflavone 7-<i>O-β</i>-<span style="font-variant: small-caps;">d</span>-apiofuranosyl-(1→6)-β-<span style="font-variant: small-caps;">d</span>-glucopyranoside (D50) with the binding affinity value of −11.35 kcal mol<sup>−1</sup>. For the target protein PDE4B, compound D50 exhibited the strongest binding affinity value of −13.01 kcal mol<sup>−1</sup>, while showing poorer inhibition ability for PDE4D. The 100 ns MD simulation examination (radius of gyration, Solvent Accessible Surface Area (SASA), Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), and hydrogen bonding) was carried out to examine the overall stability and binding efficiency of the protein–ligand complex between compounds (Millesianin F, Millesianin G, Claclrastin-7-<i>O-β</i>-<span style="font-variant: small-caps;">d</span>-glucopyranoside, 7-hydroxy-4′,6 dimethoxyisoflavone-7-<i>O-β</i>-<span style="font-variant: small-caps;">d</span>-apiofuranosyl-(1→6)-<i>β</i>-<span style="font-variant: small-caps;">d</span>-glucopyranoside, 7-hydroxy-4′,8-dimethoxyisoflavone 7-<i>O-β</i>-<span style="font-variant: small-caps;">d</span>-apiofuranosyl-(1→6)-β-<span style="font-variant: small-caps;">d</span>-glucopyranoside, Odoratin-7-<i>O-β</i>-<span style="font-variant: small-caps;">d</span>-glucopyranoside, and 5,7,4′-trihydroxyisoflavone 7-<i>O-β</i>-<span style="font-variant: small-caps;">d</span>-apiofuranosyl-(1→6)-<i>β</i>-<span style="font-variant: small-caps;">d</span>-glucopyranoside) and PDE4 (A, B) subtype proteins. Compound D50 has shown strong <i>anti</i>-inflammatory activity, as evidenced by experimental results. It effectively inhibits PDE4B and PDE4D, with IC<sub>50</sub> values of 6.56 ± 0.7 µM and 11.74 ± 1.3 µM, respectively. Additionally, it reduces NO production, with an IC<sub>50</sub> value of 5.40 ± 0.9 µM. Based on these findings, it is promising and considered a potential novel <i>anti</i>-inflammatory drug for future development.https://www.mdpi.com/1420-3049/28/21/7253<i>Millettia dielsiana</i>phosphodiesterase-4 inhibitors<i>anti</i>-inflammatoryMD modeling |
| spellingShingle | Vu Thi Thu Le Hoang Van Hung Nguyen Xuan Ha Cao Hong Le Pham Thi Hong Minh Do Tien Lam Natural Phosphodiesterase-4 Inhibitors with Potential <i>Anti</i>-Inflammatory Activities from <i>Millettia dielsiana</i> Molecules <i>Millettia dielsiana</i> phosphodiesterase-4 inhibitors <i>anti</i>-inflammatory MD modeling |
| title | Natural Phosphodiesterase-4 Inhibitors with Potential <i>Anti</i>-Inflammatory Activities from <i>Millettia dielsiana</i> |
| title_full | Natural Phosphodiesterase-4 Inhibitors with Potential <i>Anti</i>-Inflammatory Activities from <i>Millettia dielsiana</i> |
| title_fullStr | Natural Phosphodiesterase-4 Inhibitors with Potential <i>Anti</i>-Inflammatory Activities from <i>Millettia dielsiana</i> |
| title_full_unstemmed | Natural Phosphodiesterase-4 Inhibitors with Potential <i>Anti</i>-Inflammatory Activities from <i>Millettia dielsiana</i> |
| title_short | Natural Phosphodiesterase-4 Inhibitors with Potential <i>Anti</i>-Inflammatory Activities from <i>Millettia dielsiana</i> |
| title_sort | natural phosphodiesterase 4 inhibitors with potential i anti i inflammatory activities from i millettia dielsiana i |
| topic | <i>Millettia dielsiana</i> phosphodiesterase-4 inhibitors <i>anti</i>-inflammatory MD modeling |
| url | https://www.mdpi.com/1420-3049/28/21/7253 |
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