Academic Journal
Synthesis and neuroprotective activity evaluation of diosgenin derivatives based on a biocatalytic-chemosynthetic combinatorial strategy.
| Τίτλος: | Synthesis and neuroprotective activity evaluation of diosgenin derivatives based on a biocatalytic-chemosynthetic combinatorial strategy. |
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| Συγγραφείς: | Li C; The Affiliated People's Hospital, College of Integrative Medicine, Fujian-Hong Kong-Macau-Taiwan Collaborative Laboratory for the Inheritance and Innovation of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China., Sun J; Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China., Han J; The Affiliated People's Hospital, College of Integrative Medicine, Fujian-Hong Kong-Macau-Taiwan Collaborative Laboratory for the Inheritance and Innovation of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China., Lin Y; Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China., Fan R; Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China., Yang J; Yichang Humanwell Pharmaceutical CO., LTD., Yichang, 443000, China., Feng Y; The Affiliated People's Hospital, College of Integrative Medicine, Fujian-Hong Kong-Macau-Taiwan Collaborative Laboratory for the Inheritance and Innovation of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China. Electronic address: 2022029@fjtcm.edu.cn., Xu W; Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China; Fujian Health College, Fuzhou, Fujian, 350101, China. Electronic address: 2000017@fjtcm.edu.cn., Li H; Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China. Electronic address: lihua@fjtcm.edu.cn., Xu S; Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China. Electronic address: xushaohua@fjtcm.edu.cn. |
| Πηγή: | European journal of medicinal chemistry [Eur J Med Chem] 2026 Jul 05; Vol. 311, pp. 118825. Date of Electronic Publication: 2026 Apr 02. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 0420510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1768-3254 (Electronic) Linking ISSN: 02235234 NLM ISO Abbreviation: Eur J Med Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Paris : Editions Scientifiques Elsevier Original Publication: Paris, S.E.C.T. [etc.] |
| Ιατρικοί όροι (MeSH): | Diosgenin*/pharmacology , Diosgenin*/chemical synthesis , Diosgenin*/chemistry , Diosgenin*/metabolism , Neuroprotective Agents*/pharmacology , Neuroprotective Agents*/chemical synthesis , Neuroprotective Agents*/chemistry , Neuroprotective Agents*/metabolism, Apoptosis/drug effects ; Neurons/drug effects ; Signal Transduction/drug effects ; Animals ; Biocatalysis ; Structure-Activity Relationship ; Molecular Structure ; Dose-Response Relationship, Drug ; Humans |
| Περίληψη: | The natural steroidal compound diosgenin possesses neuroprotective pharmacological activity. To obtain compounds with enhanced activity, this study, based on the molecular hybridization strategy, firstly synthesized a series of C-3 position substituted derivatives (DG1-DG15) via esterification reactions between diosgenin and cinnamic acid derivatives. Given the limited modifiable sites on diosgenin, this study then innovatively combined biotransformation and chemical semi-synthesis for its structural modification, integrating the high regio- and stereoselectivity of biocatalysis with the flexibility of chemical synthesis. The newly introduced hydroxyl group by biotransformation served as a versatile handle to install various functional groups at the C-7 position through simple chemical reactions. Consequently, a series of C-7 substituted derivatives (DG16-DG24) and novel C-3,7 disubstituted derivatives (DG25-DG33) were obtained. In vitro cell experiments identified candidate compound DG23 as exhibiting the superior activity. Further mechanistic studies indicated that DG23 likely exerts its neuroprotective effects by inhibiting neuronal apoptosis through the AKT/mTOR and JAK2/STAT3 signaling pathways. (Copyright © 2026 Elsevier Masson SAS. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: AKT; Biocatalytic–chemosynthetic combinatorial strategy; Diosgenin derivatives; Neuroprotective; STAT3 |
| Substance Nomenclature: | K49P2K8WLX (Diosgenin) 0 (Neuroprotective Agents) |
| Entry Date(s): | Date Created: 20260405 Date Completed: 20260714 Latest Revision: 20260714 |
| Update Code: | 20260715 |
| DOI: | 10.1016/j.ejmech.2026.118825 |
| PMID: | 41936800 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1768-3254 |
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| DOI: | 10.1016/j.ejmech.2026.118825 |