The production of fungal metabolites can be remarkably influenced by various cultivation parameters. To explore the biosynthetic potentials of the marine fungus, Neosartorya pseudofischeri, which was isolated from the inner tissue of starfish Acanthaster planci, glycerol-peptone-yeast extract (GlyPY) and glucose-peptone-yeast extract (GluPY) media were used to culture this fungus. When cultured in GlyPY medium, this fungus produced two novel diketopiperazines, neosartins A and B (1 and 2), together with six biogenetically-related known diketopiperazines,1,2,3,4-tetrahydro-2, 3-dimethyl-1,4-dioxopyrazino[1,2-a]indole (3), 1,2,3,4-tetrahydro-2-methyl-3-methylen e-1,4-dioxopyrazino[1,2-a]indole (4), 1,2,3,4-tetrahydro-2-methyl-1,3,4-trioxopyrazino[1,2-a] indole (5), 6-acetylbis(methylthio)gliotoxin (10), bisdethiobis(methylthio)gliotoxin (11), didehydrobisdethiobis(methylthio)gliotoxin (12) and N-methyl-1H-indole-2-carboxamide (6). However, a novel tetracyclic-fused alkaloid, neosartin C (14), a meroterpenoid, pyripyropene A (15), gliotoxin (7) and five known gliotoxin analogues, acetylgliotoxin (8), reduced gliotoxin (9), 6-acetylbis(methylthio)gliotoxin (10), bisdethiobis(methylthio) gliotoxin (11) and bis-N-norgliovictin (13), were obtained when grown in glucose-containing medium (GluPY medium). This is the first report of compounds 3, 4, 6, 9, 10 and 12 as naturally occurring. Their structures were determined mainly by MS, 1D and 2D NMR data. The possible biosynthetic pathways of gliotoxin-related analogues and neosartin C were proposed. The antibacterial activity of compounds 2–14 and the cytotoxic activity of compounds 4, 5 and 7–13 were evaluated. Their structure-activity relationships are also preliminarily discussed.

Two novel isobenzofuranone derivatives, pseudaboydins A (1) and B (2), along with five known compounds, including (R)-2-(2-hydroxypropan-2-yl)-2,3-dihydro-5-hydroxybenzofuran (3), (R)-2-(2-hydroxypropan-2-yl)-2,3-dihydro-5-methoxybenzofuran (4), 3,3′-dihydroxy-5,5′-dimethyldiphenyl ether (5), 3-(3-methoxy-5-methylphenoxy)-5-methylphenol (6) and (−)-regiolone (7), were isolated from the culture broth of the marine fungus, Pseudallescheria boydii, associated with the starfish, Acanthaster planci. Their structures were elucidated primarily based on NMR and MS data. The absolute configurations of 1–4 were determined by CD spectroscopy and single-crystal X-ray diffraction studies. The cytotoxic and antibacterial activities of 1–4 were evaluated. Pseudaboydin A (1) showed moderate cytotoxic activity against human nasopharyngeal carcinoma cell line HONE1, human nasopharyngeal carcinoma cell line SUNE1 and human glandular lung cancer cell line GLC82 with IC₅₀ values of 37.1, 46.5 and 87.2 μM, respectively.

Two aromadendrane-type sesquiterpene diastereomers pseuboydones A, B (1, 2), two diketopiperazines pseuboydones C, D (3, 4), and a cyclopiazonic acid analogue pseuboydone E (13) together with twenty known compounds (5–12, 14–25) were isolated from the culture broth of the marine-derived fungus associated with the soft coral Lobophytum crassum. The twenty-five compounds in total belong to diverse structural classes, including sesquiterpenoids, diketopiperazines, alkaloids, meroterpenoids, pyrazines, and polyketides. The structures of the new compounds were elucidated using HRMS, 1D and 2D NMR spectroscopic data, ECD calculations, and X-ray single crystal diffraction analysis. Compounds 3, 11, 16, 17, and 18 displayed significant cytotoxicity against the Sf9 cells from the fall armyworm Spodoptera frugiperda.

药物性胆汁淤积(drug-induced cholestasis, DIC)是指由各类处方或非处方的化学药物, 生物制剂, 传统中药, 天然药及其代谢产物等所引发的胆汁分泌或排泄障碍而导致胆酸在肝组织或循环系统内的蓄积. 近年来, 随着人口老龄化与临床用药种类及联合用药的比例增加, 作为药物性肝损伤(drug-induced liver injury, DILI)常见表现形式的DIC的发病率逐年上升, 已引起包括临床药师在内的医务工作者的广泛关注. DIC所致的肝损伤是一个复杂的过程, 主要被两类生物反应所触发: 胆酸蓄积所导致的损害性反应, 以及机体旨在清除蓄积胆酸的适应性反应. DIC涉及的机制涉及转运蛋白, 肝细胞, 胆小管等功能或微观结构的改变. DIC目前仍然缺乏特效的治疗方法, 发现可疑导致DIC药物时, 及时停用, 根据DIC的临床症状选用合适的药物缓解, 极少数进展至肝衰竭的重症患者者可考虑肝移植以挽救生命. 对DIC发生机制的准确理解有助于新药开发与上市后体内DILI预测与预警模型的优化, 推动防治方案的完善与相关干预药物的研发. 本文综述DIC的病理发生机制与防治研究进展, 以期为DIC后续的深入研究提供参考.