Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Mar Drugs. 2018 Jul 7;16(7):230. doi: 10.3390/md16070230.
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 (⁻) and six known compounds (, , and ⁻), were obtained from the coral-derived fungus . 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 ⁻ were evaluated for the immunosuppressive activity, and ⁻ showed potent IMPDH2 inhibitory potency with IC values of 0.84⁻0.95 μM, which were comparable to that of MPA (the positive control), while ⁻ showed significant inhibitory potency with IC 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.
麦考酚酸（MPA）是一种有效的肌苷-5'-单磷酸脱氢酶（IMPDH）抑制剂，用于免疫抑制化疗。最重要的是，作为 MPA 的 2-吗啉乙基酯前药，吗替麦考酚酯（MMF）是一种用于预防器官移植排斥反应的知名免疫抑制剂。然而，由于其频繁发生的副作用，人们仍在寻找新的治疗药物。在我们目前的工作中，通过有效的基于生物测定的分级和纯化，从珊瑚来源的真菌中获得了 11 种麦考酚酸衍生物，包括 5 种以前未报道的代谢物（⁻）和 6 种已知化合物（，，和 ⁻）。它们的结构通过广泛的光谱分析（包括 1D 和 2D NMR 和 HRESIMS 数据）以及与文献中报道的已知化合物的 NMR 和其他物理数据的比较来阐明。所有分离物 ⁻都评估了免疫抑制活性， ⁻对 IMPDH2 具有很强的抑制活性，IC 值为 0.84⁻0.95 μM，与 MPA（阳性对照）相当，而 ⁻对 IMPDH2 具有显著的抑制活性，IC 值为 3.27⁻24.68 μM。所有 MPA 衍生物均表现出有希望的免疫抑制活性，使它们成为器官移植和自身免疫相关疾病的潜在药物先导物。
