Artematrovirenolides A—D and Artematrolides S—Z, Sesquiterpenoid Dimers with Cytotoxicity against Three Hepatoma Cell Lines from Artemisia atrovirens

• Published in: Chinese journal of chemistry Vol. 40; no. 1; pp. 104 - 114
• Main Authors: Su, Li‐Hua, Li, Tian‐Ze, Ma, Yun‐Bao, Geng, Chang‐An, Huang, Xiao‐Yan, Zhang, Xin, Gao, Zhen, Chen, Ji‐Jun
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH & Co. KGaA 01.01.2022; Wiley; Wiley Subscription Services, Inc
• Subjects: Absolute configuration; Adducts; Antihepatoma activity; Artemisia atrovirens; Biocompatibility; Biological activity; Cell lines; Chemistry; Chemistry, Multidisciplinary; Crystal structure; Cycloaddition; Cytotoxicity; Dimers; Hepatoma; Physical Sciences; Science & Technology; Sesquiterpenoid dimers; Single crystals; Structure elucidation; Toxicity; X‐ray diffraction; Artemisia atrovirens; Antihepatoma activity; NATURAL DISESQUITERPENOIDS; Sesquiterpenoid dimers; X-ray diffraction; GUAIANOLIDE; ARGYI; Structure elucidation
• ISSN: 1001-604X; 1614-7065
• DOI: 10.1002/cjoc.202100528

Comprehensive Summary Inspired by the intriguing structures and remarkable activities of sesquiterpenoid dimers, 12 new sesquiterpenoid dimers, artematrovirenolides A—D (1—4) and artematrolides S—Z (8—12), were isolated from the EtOAc fraction of Artemisia atrovirens through a bioactivity‐guided approach. Their structures were elucidated by comprehensive spectroscopic data and absolute configuration was assigned based on single crystal X‐ray diffraction data and ECD calculations. Structurally, all compounds are presumably formed via [4+2] cycloaddition involving three connecting model. Compounds 1—4 are four novel hetero‐dimeric [4+2] Diels–Alder adducts dimerized from a rotundane‐type unit and a guaiane‐type monomer, and compounds 5—12 are eight new homo‐dimeric [4+2] adducts derived from two guaianolide moieties. A putative biosynthetic pathway for compounds 1—4 was also proposed. Compounds 4, 6, 7, and 10 demonstrated moderate cytotoxicity against HepG2, SMMC‐7721, and Huh7 cell lines with IC50 values ranging from 9.3 to 62.3 μmol/L. Interestingly, compounds 5 and 11 manifested cytotoxicity with IC50 values of 13.6 and 12.8 (HepG2), 18.5 and 13.1 (SMMC‐7721), and 16.5 and 19.4 μmol/L (Huh7), respectively, which were equivalent to the positive control, sorafenib. This investigation suggests that compounds 5 and 11 might be considered as potent antihepatoma candidates and deserve further structural modification and mechanism study. Twelve new sesquiterpenoid dimers were isolated from A. atrovirens. The absolute stereochemistry of compounds 1, 2, 5, 8, and 9 were determined by single‐crystal X‐ray diffraction analyses. Compounds 5 and 11 manifested cytotoxicity with IC50 values of 13.6 and 12.8 μmol/L (HepG2), 18.5 and 13.1 μmol/L (SMMC‐7721), and 16.5 and 19.4 μmol/L (Huh7), respectively, which were equivalent to the positive control, sorafenib.