Zhai Xin-Yi, Liu Jin-Jie, Wang Cui-Duan, Dou Yi-Fan, Lv Jian-Hua, Wang Li-An, Zhang Jin-Xiu, Li Zhuang
College of Life Sciences, Hebei Normal University, Shijiazhuang, 050000, People's Republic of China.
School of Land Science and Space Planning, Hebei GEO University, Shijiazhuang, 050000, People's Republic of China.
Nat Prod Bioprospect. 2025 Jul 18;15(1):46. doi: 10.1007/s13659-025-00530-x.
Seven previously undescribed polycyclic meroterpenoids talarines K-Q (1-7), along with five known ones (8-12), were isolated from desert-derived fungi Talaromyces sp. HMT-8. The structure of the novel compounds were elucidated using spectroscopic methods, including electronic circular dichroism (ECD), HRESIMS and nuclear magnetic resonance (NMR) spectroscopy. Among the isolated meroterpenoids, compounds 3, 5, and 7 exhibited rare chlorine substitution patterns. Halogenation, particularly chlorination, is uncommon in natural meroterpenoids and implies the involvement of halogenase enzymes during biosynthesis. Compounds 1-12 were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Compounds 1-4 and 12 exhibited inhibitory activity against PTP1B with IC₅₀ values ranging from 1.74 to 17.60 μM. Among them, compounds 2 and 12 displayed significant inhibitory effects with an IC₅₀ value of 1.74 and 3.03 μM, respectively. Furthermore, Molecular docking analysis revealed that compounds 2 and 12 bind tightly to the catalytic site of PTP1B, forming key hydrogen bonding and hydrophobic interactions. Enzyme kinetics studies further demonstrated that both compounds act as competitive inhibitor.
从源自沙漠的真菌特异青霉属菌株HMT-8中分离出7个前所未描述的多环半萜类化合物塔拉灵K-Q（1-7），以及5个已知化合物（8-12）。采用电子圆二色光谱（ECD）、高分辨电喷雾电离质谱（HRESIMS）和核磁共振（NMR）光谱等光谱方法阐明了这些新化合物的结构。在分离得到的半萜类化合物中，化合物3、5和7呈现出罕见的氯取代模式。卤化，尤其是氯化，在天然半萜类化合物中并不常见，这意味着在生物合成过程中有卤化酶的参与。对化合物1-12进行了蛋白酪氨酸磷酸酶1B（PTP1B）抑制活性评价。化合物1-4和12对PTP1B表现出抑制活性，IC₅₀值在1.74至17.60 μM之间。其中，化合物2和12表现出显著的抑制作用，IC₅₀值分别为1.74和3.03 μM。此外，分子对接分析表明，化合物2和12与PTP1B的催化位点紧密结合，形成关键的氢键和疏水相互作用。酶动力学研究进一步证明这两种化合物均为竞争性抑制剂。
