Pema-Tenzin Puno

Arthrinium species are promising producers of terpenoids with diverse architectures and noteworthy pharmacological properties. In this work, ten undescribed terpestacin-type sesterterpenoids, arthritacins A–J (1–10), together with five known analogues (11–15), were obtained from the endophytic fungus Arthrinium sp. HS66 isolated from the stems of Isodon xerophilus. Their structures were established through comprehensive spectroscopic analysis, semisynthesis, and NMR calculations, further supported by DP4+ probability analysis. The semisynthetic studies further helped confirm the biosynthetically ambiguous configurations at C-11 and C-23 in terpestacin derivatives. All compounds were evaluated for cytotoxic activity against human neuroblastoma cells. Among them, compounds 1, 2, 4, 6, 7, 9, 12 and 13 showed moderate antiproliferative effects, with IC₅₀ values ranging from 21.13 to 36.54 µM.

Twenty new lanostane triterpenoids, kadsuracoccinins A–T (1–20, respectively), were isolated from the stems of Kadsura coccinea, with compounds 1–7 constituting four new carbon scaffolds elucidated by NMR analysis, X-ray diffraction, GEMSTONE-NOE-aided fc-rDG/DDD, and ECD calculations. Luciferase-refolding, NMR STD, and SPR assays revealed compounds 4 and 8–10 as the first lanostane-type Hsp90 inhibitors, which bind Hsp90 through non-N-terminal modes, with compound 8 exhibiting a KD of 4.04 μM.

Three new triterpenoids, henridilactones P–R ( 1 – 3 ) and two new dibenzocyclooctadiene lignans, henrilignans A and B ( 11 and 12 ), alongside twelve known analogues ( 4 – 10 and 13 – 17 ) were isolated from the stems and leaves of Schisandra henryi subsp. yunnanensis . The structures and absolute configurations of new compounds were elucidated by comprehensive 1D and 2D NMR, HRESIMS, electronic circular dichroism analyses, and theoretical calculations. In bioactivity evaluation, the isolated triterpenoids ( 1 – 10 ) exhibited moderate neurite outgrowth in differentiated PC12 cells at 10 µM (differentiation rates 10.09%–12.96%; positive control 50 ng/mL NGF, 19.71%). Furthermore, henridilactone P ( 1 ) exhibited a binding affinity with an equilibrium dissociation constant ( K _D ) of 3.286 × 10 ^{− 4} M (reference compound PF‐06446846, K _D = 8.008 × 10 ^{− 5} M).

Natural products (NPs) are invaluable resources for drug discovery, characterized by their intricate scaffolds and diverse bioactivities. AI drug discovery & design (AIDD) has emerged as a transformative approach for the rational structural modification of NPs. This review examines a variety of molecular generation models since 2020, focusing on their potential applications in two primary scenarios of NPs structure modification: modifications when the target is identified and when it remains unidentified. Most of the molecular generative models discussed herein are open-source, and their applicability across different domains and technical feasibility have been evaluated. This evaluation was accomplished by integrating a limited number of research cases and successful practices observed in the molecular optimization of synthetic compounds. Furthermore, the challenges and prospects of employing molecular generation modeling for the structural modification of NPs are discussed. Graphical Abstract

为进一步阐明中药冬凌草的药效物质基础，综合采用多种柱色谱分离技术从山西省绛县产冬凌草中分离得到5个新的对映-贝壳杉烷二萜isojiangrubesins H–L (1–5)和2个已知二萜rubescensin N (6)和xerophilusin B (7). 通过高分辨质谱和核磁等波谱解析技术对化合物结构进行了鉴定. 抗肿瘤活性筛选表明, 化合物3、4和7对人结肠癌细胞SW480表现出显著的细胞毒活性, IC₅₀值为1.03–7.14 μM.

The asymmetric total synthesis of penicifuranone A was achieved in eight steps using an NHC-catalyzed umpolung strategy. This approach enabled a convergent formal [4 + 2] annulation with gregatin A, leading to penicifuranone A.

Aurantiacin A (1), a unique ascorbylated meroditerpenoid composed of an unusual 9-epi-spiro-lactone-type ent-kaurane diterpenoid core, ascorbic acid (vitamin C), and syringic acid, and three new 9-epi-spiro-lactone-type ent-kauranoids, aurantiacins B-D (2-4), were isolated from an untapped species, Isodon aurantiacus. Their structures were determined by spectroscopic data analysis, semisynthesis, floating chirality distance geometry calculations, and quantum chemical calculations. Aurantiacin A (1) was found to induce lysosomal biogenesis, and the potential mechanisms underlying this effect were preliminarily explored.