Phomaderide, a unique (6/5/4/5/6) spiro-cyclic dimer from the desert plant endophytic fungus Phoma betae A. B. Frank (Didymellaceae)
IntroductionEndophytic fungi from desert plants are prolific producers of structurally unique stress-responsive metabolites. This study investigates the secondary metabolites of Phoma betae A. B. Frank (Didymellaceae), a desert plant endophytic fungus, aiming to discover novel bioactive compounds th...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2025.1583666/full |
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| author | Hao-Di Sun Yan-Duo Wang Hui-Qi Fang Jian Yang Yu-Tong Hua Gang Ding Lan-Ping Guo |
| author_facet | Hao-Di Sun Yan-Duo Wang Hui-Qi Fang Jian Yang Yu-Tong Hua Gang Ding Lan-Ping Guo |
| author_sort | Hao-Di Sun |
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| description | IntroductionEndophytic fungi from desert plants are prolific producers of structurally unique stress-responsive metabolites. This study investigates the secondary metabolites of Phoma betae A. B. Frank (Didymellaceae), a desert plant endophytic fungus, aiming to discover novel bioactive compounds through advanced molecular networking strategies.MethodsA building blocks-based molecular network (BBMN) strategy was employed to screen the fungal extract. Target compounds were isolated using silica gel and ODS column chromatography, followed by semi-preparative HPLC purification. Structural elucidation was achieved through comprehensive NMR spectroscopy, mass fragmentation pathway analysis, and electronic circular dichroism (ECD) calculations. Cytotoxicity was evaluated against HeLa and A549 cancer cell lines using CCK-8 assays.ResultsThree compounds were characterized:Phomaderide (3), a unique (6/5/4/5/6) spiro-cyclic dimer formed via stereoselective [2+2] photocycloaddition of two phaeosphaeride A (1) monomers. Its biosynthetic precursor phaeosphaeride A (1). A new hydroxylated analog, phaeosphaeride C (2). Compounds 2 and 3 exhibited moderate cytotoxicity against HeLa (IC50 29.97–39.15 μM) and A549 cells (IC50 30.47–58.33 μM).DiscussionThis work highlights the metabolic versatility of extremophilic fungi, demonstrating Phoma betae's capacity to generate architecturally complex molecules. Phomaderide's unprecedented spiro-cyclic dimer scaffold positions it as a promising lead for anticancer drug discovery, with structural modifications (hydroxylation and dimerization) significantly influencing bioactivity. The BBMN strategy proved effective for targeted isolation of structurally related analogs from complex extracts. |
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| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Chemistry |
| spelling | doaj-art-3a15b1c194264e549c48c6e16a70d0f72025-07-07T05:26:27ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462025-07-011310.3389/fchem.2025.15836661583666Phomaderide, a unique (6/5/4/5/6) spiro-cyclic dimer from the desert plant endophytic fungus Phoma betae A. B. Frank (Didymellaceae)Hao-Di Sun0Yan-Duo Wang1Hui-Qi Fang2Jian Yang3Yu-Tong Hua4Gang Ding5Lan-Ping Guo6State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences, China Academy of Chinese Medical Sciences, Beijing, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences, China Academy of Chinese Medical Sciences, Beijing, ChinaIntroductionEndophytic fungi from desert plants are prolific producers of structurally unique stress-responsive metabolites. This study investigates the secondary metabolites of Phoma betae A. B. Frank (Didymellaceae), a desert plant endophytic fungus, aiming to discover novel bioactive compounds through advanced molecular networking strategies.MethodsA building blocks-based molecular network (BBMN) strategy was employed to screen the fungal extract. Target compounds were isolated using silica gel and ODS column chromatography, followed by semi-preparative HPLC purification. Structural elucidation was achieved through comprehensive NMR spectroscopy, mass fragmentation pathway analysis, and electronic circular dichroism (ECD) calculations. Cytotoxicity was evaluated against HeLa and A549 cancer cell lines using CCK-8 assays.ResultsThree compounds were characterized:Phomaderide (3), a unique (6/5/4/5/6) spiro-cyclic dimer formed via stereoselective [2+2] photocycloaddition of two phaeosphaeride A (1) monomers. Its biosynthetic precursor phaeosphaeride A (1). A new hydroxylated analog, phaeosphaeride C (2). Compounds 2 and 3 exhibited moderate cytotoxicity against HeLa (IC50 29.97–39.15 μM) and A549 cells (IC50 30.47–58.33 μM).DiscussionThis work highlights the metabolic versatility of extremophilic fungi, demonstrating Phoma betae's capacity to generate architecturally complex molecules. Phomaderide's unprecedented spiro-cyclic dimer scaffold positions it as a promising lead for anticancer drug discovery, with structural modifications (hydroxylation and dimerization) significantly influencing bioactivity. The BBMN strategy proved effective for targeted isolation of structurally related analogs from complex extracts.https://www.frontiersin.org/articles/10.3389/fchem.2025.1583666/fullphomaderidedesert plant endophytic fungusbuilding block-based molecular networkcytotoxicitystructural elucidationnatural products |
| spellingShingle | Hao-Di Sun Yan-Duo Wang Hui-Qi Fang Jian Yang Yu-Tong Hua Gang Ding Lan-Ping Guo Phomaderide, a unique (6/5/4/5/6) spiro-cyclic dimer from the desert plant endophytic fungus Phoma betae A. B. Frank (Didymellaceae) Frontiers in Chemistry phomaderide desert plant endophytic fungus building block-based molecular network cytotoxicity structural elucidation natural products |
| title | Phomaderide, a unique (6/5/4/5/6) spiro-cyclic dimer from the desert plant endophytic fungus Phoma betae A. B. Frank (Didymellaceae) |
| title_full | Phomaderide, a unique (6/5/4/5/6) spiro-cyclic dimer from the desert plant endophytic fungus Phoma betae A. B. Frank (Didymellaceae) |
| title_fullStr | Phomaderide, a unique (6/5/4/5/6) spiro-cyclic dimer from the desert plant endophytic fungus Phoma betae A. B. Frank (Didymellaceae) |
| title_full_unstemmed | Phomaderide, a unique (6/5/4/5/6) spiro-cyclic dimer from the desert plant endophytic fungus Phoma betae A. B. Frank (Didymellaceae) |
| title_short | Phomaderide, a unique (6/5/4/5/6) spiro-cyclic dimer from the desert plant endophytic fungus Phoma betae A. B. Frank (Didymellaceae) |
| title_sort | phomaderide a unique 6 5 4 5 6 spiro cyclic dimer from the desert plant endophytic fungus phoma betae a b frank didymellaceae |
| topic | phomaderide desert plant endophytic fungus building block-based molecular network cytotoxicity structural elucidation natural products |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2025.1583666/full |
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