Academic Journal
Tolypaxillines A-J: indole diterpenoids with neuroprotective activities from a soil-derived fungus Tolypocladium album DWS131.
| Title: | Tolypaxillines A-J: indole diterpenoids with neuroprotective activities from a soil-derived fungus Tolypocladium album DWS131. |
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| Authors: | Tan YF; Department of Pharmacy, National Clinical Research Center for Geriatric Disease, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China; The Hunan Institute of Pharmacy Practice and Clinical Research, Changsha, 410008, PR China., Chen XY; Eye Center of Xiangya Hospital, Central South University, Changsha, 410008, PR China; Hunan Key Laboratory of Ophthalmology, Changsha, 410008, PR China., Wang C; Eye Center of Xiangya Hospital, Central South University, Changsha, 410008, PR China; Hunan Key Laboratory of Ophthalmology, Changsha, 410008, PR China., Liang AL; Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, PR China., Lu WY; Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, PR China., Feng LM; Eye Center of Xiangya Hospital, Central South University, Changsha, 410008, PR China; Hunan Key Laboratory of Ophthalmology, Changsha, 410008, PR China., Huang Q; Department of Pharmacy, National Clinical Research Center for Geriatric Disease, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China; The Hunan Institute of Pharmacy Practice and Clinical Research, Changsha, 410008, PR China., Jiang YP; Department of Pharmacy, National Clinical Research Center for Geriatric Disease, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China; The Hunan Institute of Pharmacy Practice and Clinical Research, Changsha, 410008, PR China., Liu S; Department of Pharmacy, National Clinical Research Center for Geriatric Disease, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China; The Hunan Institute of Pharmacy Practice and Clinical Research, Changsha, 410008, PR China., Xia XB; Eye Center of Xiangya Hospital, Central South University, Changsha, 410008, PR China; Hunan Key Laboratory of Ophthalmology, Changsha, 410008, PR China., Li J; Department of Pharmacy, National Clinical Research Center for Geriatric Disease, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China; The Hunan Institute of Pharmacy Practice and Clinical Research, Changsha, 410008, PR China. Electronic address: lijingliyun@csu.edu.cn., Wang WX; Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, PR China. Electronic address: wangwenxuan@csu.edu.cn. |
| Source: | Phytochemistry [Phytochemistry] 2026 Jul; Vol. 247, pp. 114855. Date of Electronic Publication: 2026 Mar 06. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: England NLM ID: 0151434 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3700 (Electronic) Linking ISSN: 00319422 NLM ISO Abbreviation: Phytochemistry Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2003- : London : Elsevier Original Publication: 1961-2003: Oxford : Pergamon Press. |
| MeSH Terms: | Diterpenes*/chemistry , Diterpenes*/pharmacology , Diterpenes*/isolation & purification , Neuroprotective Agents*/chemistry , Neuroprotective Agents*/pharmacology , Neuroprotective Agents*/isolation & purification , Indoles*/chemistry , Indoles*/pharmacology , Indoles*/isolation & purification , Hypocreales*/chemistry, Glutamic Acid/pharmacology ; Animals ; Molecular Structure ; Rats ; Soil Microbiology ; Structure-Activity Relationship ; Dose-Response Relationship, Drug |
| Abstract: | Ten previously undescribed indole diterpenoids, tolypaxillines A-J, were isolated from a culture of the soil-derived fungus Tolypocladium album DWS131, along with six known analogs. Their structures were determined by 1D/2D NMR, HRESIMS, electronic circular dichroism calculation, and NMR data comparison with known compounds. Tolypaxilline A, tolypaxilline B, and shearinine PC feature an eight-membered ketoamide ring within a previously unreported 6/8/6/6/6 pentacyclic skeleton. Tolypaxillines C-I are characterized as seven-membered indole diterpenoids featuring a 6/5/5/6/6/6/5 heptacyclic framework. Notably, tolypaxilline J is a rare indole diterpenoid with an eight-membered ketoamide-opening motif. The in vitro neuroprotective activities of the isolated compounds were evaluated using the glutamate-induced R28 cell excitotoxicity model, with compounds tolypaxilline C, tolypaxilline F, paxilline, 7-hydroxypaxilline-13-ene, and PC-M6 showing significant protective effects, among which paxilline was the most potent. Remarkably, paxilline also demonstrated protective activity in the in vivo N-methyl-d-aspartate-induced retinal injury model. Further investigation into the mode of action revealed that paxilline inhibits ferroptosis by modulating the SLC7A11/GPX4 signaling pathway, suggesting its potential as a retinal protective agent. (Copyright © 2026 Elsevier Ltd. 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: Ferroptosis; Indole diterpenoids; Neuroprotective activities; Ophiocordycipitaceae; Tolypocladium album |
| Substance Nomenclature: | 0 (Diterpenes) 0 (Neuroprotective Agents) 0 (Indoles) 3KX376GY7L (Glutamic Acid) |
| Entry Date(s): | Date Created: 20260309 Date Completed: 20260710 Latest Revision: 20260710 |
| Update Code: | 20260711 |
| DOI: | 10.1016/j.phytochem.2026.114855 |
| PMID: | 41796825 |
| Database: | MEDLINE |
| ISSN: | 1873-3700 |
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| DOI: | 10.1016/j.phytochem.2026.114855 |