Artemselenoids A-H, eight guaiane-type sesquiterpenoid dimers from Artemisia selengensis and their antihepatoma activities

• Published in: Organic & biomolecular chemistry Vol. 23; no. 13; pp. 3183 - 3193
• Main Authors: Chen, Rong-Kai, Li, Tian-Ze, Ma, Yun-Bao, Wang, Yong-Cui, Chen, Ji-Jun
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 26.03.2025; Royal Society of Chemistry
• Subjects: Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Artemisia - chemistry; Artemisia selengensis; Cell Line, Tumor; Cell lines; Chemical bonds; Chemistry; Chemistry, Organic; Cycloaddition; Dimerization; Dimers; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Hepatoma; Humans; Molecular Structure; NMR; Nuclear magnetic resonance; Physical Sciences; Science & Technology; Sesquiterpenes - chemistry; Sesquiterpenes - isolation & purification; Sesquiterpenes - pharmacology; Sesquiterpenes, Guaiane - chemistry; Sesquiterpenes, Guaiane - isolation & purification; Sesquiterpenes, Guaiane - pharmacology; Structure-Activity Relationship; NATURAL DISESQUITERPENOIDS; ASSIGNMENT
• ISSN: 1477-0520; 1477-0539; 1477-0539
• DOI: 10.1039/d5ob00222b

Eight undescribed guaiane-type sesquiterpenoid dimers (GSDs), artemselenoids A-H (1-8), together with nine known GSDs (9-17), were isolated from Artemisia selengensis. Their structures and absolute configurations were determined through comprehensive spectral analyses, theoretical ECD calculations, and NMR computations. Chemically, compound 1 represented the first example of two guaianolide lactone units dimerizing through unprecedented C-3-C-11 ' and C-4-C-13 ' bonds via a [2 + 2] cycloaddition reaction and producing a structurally unique 5,4 spirocyclic system; compounds 2-8 were biogenetically formed through a [4 + 2] cycloaddition reaction. Specifically, compounds 2-7 were connected by C-1-C-13 ' and C-4-C-11 ' bonds, while compound 8 was linked by C-1-C-13 ' and C-4-C-11 ' bonds. Antihepatoma assays indicated that the most active compounds 3 and 8 demonstrated significant inhibitory effects on three hepatoma cell lines, with IC50 values of 7.4 and 5.1 mu M (HepG2), 5.9 and 8.6 mu M (Huh7), and 20.9 and 9.6 mu M (SK-Hep-1), which were equal to those of the positive control sorafenib.