Mycophenolic Acid Derivatives with Immunosuppressive Activity from the Coral-Derived Fungus Penicillium bialowiezense
Mycophenolic acid (MPA) is a potent inosine-5′-monophosphate dehydrogenase (IMPDH) inhibitor for immunosuppressive chemotherapy. Most importantly, as the 2-morpholinoethyl ester prodrug of MPA, mycophenolate mofetil (MMF) is a well-known immunosuppressant used to prevent rejection in organ...
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MDPI AG
2018-07-01
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| author | Qing Zhang Beiye Yang Fengli Li Mengting Liu Shuang Lin Jianping Wang Yongbo Xue Hucheng Zhu Weiguang Sun Zhengxi Hu Yonghui Zhang |
| author_facet | Qing Zhang Beiye Yang Fengli Li Mengting Liu Shuang Lin Jianping Wang Yongbo Xue Hucheng Zhu Weiguang Sun Zhengxi Hu Yonghui Zhang |
| author_sort | Qing Zhang |
| collection | DOAJ |
| description | Mycophenolic acid (MPA) is a potent inosine-5′-monophosphate dehydrogenase (IMPDH) inhibitor for immunosuppressive chemotherapy. Most importantly, as the 2-morpholinoethyl ester prodrug of MPA, mycophenolate mofetil (MMF) is a well-known immunosuppressant used to prevent rejection in organ transplantations. Nevertheless, due to its frequently occurred side effects, searching for new therapeutic agents is ongoing. In our current work, by virtue of efficient bioassay-guided fractionation and purification, eleven mycophenolic acid derivatives, including five previously unreported metabolites (3–7) and six known compounds (1, 2, and 8–11), were obtained from the coral-derived fungus Penicillium bialowiezense. Their structures were elucidated by means of extensive spectroscopic analyses (including 1D and 2D NMR and HRESIMS data) and comparison of the NMR and other physical data with those reported in the literature in the case of the known compounds. All the isolates 1–11 were evaluated for the immunosuppressive activity, and 1–3 showed potent IMPDH2 inhibitory potency with IC50 values of 0.84–0.95 μM, which were comparable to that of MPA (the positive control), while 4–10 showed significant inhibitory potency with IC50 values of 3.27–24.68 μM. All the MPA derivatives showed promising immunosuppressive activity, endowing them as potential drug leads for organ transplantations and autoimmune related diseases. |
| first_indexed | 2024-04-11T13:46:03Z |
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| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T13:46:03Z |
| publishDate | 2018-07-01 |
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| series | Marine Drugs |
| spelling | doaj.art-3962e7278a3e4a42b912c654671332642022-12-22T04:21:01ZengMDPI AGMarine Drugs1660-33972018-07-0116723010.3390/md16070230md16070230Mycophenolic Acid Derivatives with Immunosuppressive Activity from the Coral-Derived Fungus Penicillium bialowiezenseQing Zhang0Beiye Yang1Fengli Li2Mengting Liu3Shuang Lin4Jianping Wang5Yongbo Xue6Hucheng Zhu7Weiguang Sun8Zhengxi Hu9Yonghui Zhang10Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaMycophenolic acid (MPA) is a potent inosine-5′-monophosphate dehydrogenase (IMPDH) inhibitor for immunosuppressive chemotherapy. Most importantly, as the 2-morpholinoethyl ester prodrug of MPA, mycophenolate mofetil (MMF) is a well-known immunosuppressant used to prevent rejection in organ transplantations. Nevertheless, due to its frequently occurred side effects, searching for new therapeutic agents is ongoing. In our current work, by virtue of efficient bioassay-guided fractionation and purification, eleven mycophenolic acid derivatives, including five previously unreported metabolites (3–7) and six known compounds (1, 2, and 8–11), were obtained from the coral-derived fungus Penicillium bialowiezense. Their structures were elucidated by means of extensive spectroscopic analyses (including 1D and 2D NMR and HRESIMS data) and comparison of the NMR and other physical data with those reported in the literature in the case of the known compounds. All the isolates 1–11 were evaluated for the immunosuppressive activity, and 1–3 showed potent IMPDH2 inhibitory potency with IC50 values of 0.84–0.95 μM, which were comparable to that of MPA (the positive control), while 4–10 showed significant inhibitory potency with IC50 values of 3.27–24.68 μM. All the MPA derivatives showed promising immunosuppressive activity, endowing them as potential drug leads for organ transplantations and autoimmune related diseases.http://www.mdpi.com/1660-3397/16/7/230coral-derived fungusPenicillium bialowiezenseMycophenolic acid derivativesimmunosuppressive activitymolecular docking |
| spellingShingle | Qing Zhang Beiye Yang Fengli Li Mengting Liu Shuang Lin Jianping Wang Yongbo Xue Hucheng Zhu Weiguang Sun Zhengxi Hu Yonghui Zhang Mycophenolic Acid Derivatives with Immunosuppressive Activity from the Coral-Derived Fungus Penicillium bialowiezense Marine Drugs coral-derived fungus Penicillium bialowiezense Mycophenolic acid derivatives immunosuppressive activity molecular docking |
| title | Mycophenolic Acid Derivatives with Immunosuppressive Activity from the Coral-Derived Fungus Penicillium bialowiezense |
| title_full | Mycophenolic Acid Derivatives with Immunosuppressive Activity from the Coral-Derived Fungus Penicillium bialowiezense |
| title_fullStr | Mycophenolic Acid Derivatives with Immunosuppressive Activity from the Coral-Derived Fungus Penicillium bialowiezense |
| title_full_unstemmed | Mycophenolic Acid Derivatives with Immunosuppressive Activity from the Coral-Derived Fungus Penicillium bialowiezense |
| title_short | Mycophenolic Acid Derivatives with Immunosuppressive Activity from the Coral-Derived Fungus Penicillium bialowiezense |
| title_sort | mycophenolic acid derivatives with immunosuppressive activity from the coral derived fungus penicillium bialowiezense |
| topic | coral-derived fungus Penicillium bialowiezense Mycophenolic acid derivatives immunosuppressive activity molecular docking |
| url | http://www.mdpi.com/1660-3397/16/7/230 |
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