Academic Journal
Cyclization, amino acid coupling, docking-based virtual screening and SAR: showing a strategy of the structural modification for salvianic acid A.
| Τίτλος: | Cyclization, amino acid coupling, docking-based virtual screening and SAR: showing a strategy of the structural modification for salvianic acid A. |
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| Συγγραφείς: | Wu J; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China.; Chinese Institutes for Medical Research, Beijing, China., Zhang X; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China., An W; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China., Yang Y; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China., Zhang P; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China., Wang Y; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China., Zhao S; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China., Feng Q; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China., Zhao M; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China., Peng S; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China. |
| Πηγή: | Future medicinal chemistry [Future Med Chem] 2026 Jun; Vol. 18 (11), pp. 1391-1403. Date of Electronic Publication: 2026 Apr 24. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Taylor & Francis Country of Publication: England NLM ID: 101511162 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1756-8927 (Electronic) Linking ISSN: 17568919 NLM ISO Abbreviation: Future Med Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2024- : [Milton Park, Oxfordshire] : Taylor & Francis Original Publication: London : Future Science, 2009- |
| Ιατρικοί όροι (MeSH): | Lactates*/chemistry , Lactates*/pharmacology , Lactates*/chemical synthesis , Lactates*/therapeutic use , Amino Acids*/chemistry , Platelet Aggregation Inhibitors*/chemistry , Platelet Aggregation Inhibitors*/pharmacology , Platelet Aggregation Inhibitors*/chemical synthesis , Molecular Docking Simulation*, Platelet Aggregation/drug effects ; Thrombosis/drug therapy ; Platelet Glycoprotein GPIIb-IIIa Complex/metabolism ; P-Selectin/blood ; Animals ; Male ; Rats ; Rats, Sprague-Dawley ; Structure-Activity Relationship ; Humans |
| Περίληψη: | Aim: Providing diverse modification remains to be a strategy for salvianic acid A. Materials and Methods: Based on the docking virtual screening, salvianic acid A was cyclized, then modified with amino acid to provide 19 derivatives (6a-s), and evaluated their effects on platelet aggregation, thrombus formation, and determine serum levels of P-selectin and GPIIb/IIIa in male SD rats. Results: The in vitro evaluation showed that 6a-s effectively against platelet-activating factor (PAF) and adenosine diphosphate (ADP) induced platelet aggregation. The in vivo anti-arterial thrombosis assay showed that 30 nmol/kg of 6a-s significantly decreased thrombus weights of rats, (3R)-6,7-dihydroxy-1,1- dimethylisochromane-3-carboxyl-Lys (6h) possessed the strongest anti-arterial thrombotic activity. The in vivo thrombolytic assay showed that the activities of 30 nmol/kg of 6a-s were significantly higher than that of saline solution (NS), 6h had the strongest activity. The ELISA assay showed that 6a-s effectively decreased the serum P-selectin and GPIIb/IIIa level. Conclusion: 6a-s can effectively inhibited PAF and ADP induced platelet aggregation in vitro, at 30 nmol/kg dose they significantly decreased the weight of thrombus and significantly increased the potential of dissolve the clots. Specially, 6h was particularly superior and could be a promising candidate for the afterward development. Additionally, the benefits of the 19 derivatives were associated with the serum level of P-selectin and GPIIb/IIIa. |
| Contributed Indexing: | Keywords: SAR; Salvianic acid A; cyclization; thrombolytic; thrombotic |
| Substance Nomenclature: | 0 (Lactates) 0 (Platelet Glycoprotein GPIIb-IIIa Complex) 0 (Amino Acids) 0 (P-Selectin) 4GF33A5PAJ (3,4-dihydroxyphenyllactic acid) 0 (Platelet Aggregation Inhibitors) |
| Entry Date(s): | Date Created: 20260424 Date Completed: 20260715 Latest Revision: 20260726 |
| Update Code: | 20260726 |
| PubMed Central ID: | PMC13228955 |
| DOI: | 10.1080/17568919.2026.2658836 |
| PMID: | 42027185 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1756-8927 |
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| DOI: | 10.1080/17568919.2026.2658836 |