Natural Phosphodiesterase-4 Inhibitors with Potential Anti-Inflammatory Activities from Millettia dielsiana
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Published:2023-10-25
Issue:21
Volume:28
Page:7253
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Le Vu Thi Thu1, Hung Hoang Van2, Ha Nguyen Xuan3, Le Cao Hong1, Minh Pham Thi Hong3, Lam Do Tien34ORCID
Affiliation:
1. Thai Nguyen University of Agriculture and Forestry, Quyet Thang, Thai Nguyen 24119, Vietnam 2. Thai Nguyen University-Lao Cai Campus, Thai Nguyen University, Lao Cai City 31000, Vietnam 3. Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi 10072, Vietnam 4. Faculty of Chemistry, Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi 10072, Vietnam
Abstract
The results of in silico screening of the 50 isolated compounds from Millettia dielsiana 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−1, respectively, with median values of −8.83, −8.84, and −8.645 kcal mol−1, 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−1). This was followed by the compound 5,7,4′-trihydroxyisoflavone 7-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (D50) with the binding affinity value of −11.35 kcal mol−1. For the target protein PDE4B, compound D50 exhibited the strongest binding affinity value of −13.01 kcal mol−1, 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-O-β-d-glucopyranoside, 7-hydroxy-4′,6 dimethoxyisoflavone-7-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside, 7-hydroxy-4′,8-dimethoxyisoflavone 7-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside, Odoratin-7-O-β-d-glucopyranoside, and 5,7,4′-trihydroxyisoflavone 7-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside) and PDE4 (A, B) subtype proteins. Compound D50 has shown strong anti-inflammatory activity, as evidenced by experimental results. It effectively inhibits PDE4B and PDE4D, with IC50 values of 6.56 ± 0.7 µM and 11.74 ± 1.3 µM, respectively. Additionally, it reduces NO production, with an IC50 value of 5.40 ± 0.9 µM. Based on these findings, it is promising and considered a potential novel anti-inflammatory drug for future development.
Funder
Ministry of Education and Training
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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