Compositacins A–K: Bioactive chamigrane-type halosesquiterpenoids from the red alga Laurencia composita Yamada

• Published in: Phytochemistry (Oxford) 2017-04, Vol.136, p.81-93
• Main Authors: Yu, Xiao-Qing, Jiang, Chang-Sheng, Zhang, Yi, Sun, Pan, Kurtán, Tibor, Mándi, Attila, Li, Xiao-Lu, Yao, Li-Gong, Liu, Ai-Hong, Wang, Bin, Guo, Yue-Wei, Mao, Shui-Chun
• Format: Article
• Language: English
• Subjects: Antifungal activity; Antifungal Agents - chemistry; Antifungal Agents - isolation & purification; Antifungal Agents - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Cell Line; Chamigrane sesquiterpenoid; Compositacins A–K; Cytotoxicity; Drug Screening Assays, Antitumor; ECD calculation; Humans; Hydrocarbons, Halogenated - chemistry; Hydrocarbons, Halogenated - isolation & purification; Hydrocarbons, Halogenated - pharmacology; Laurencia - chemistry; Laurencia composita; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Rearranged chamigrane sesquiterpenoid; Rhodomelaceae; Sesquiterpenes - chemistry; Sesquiterpenes - isolation & purification; Sesquiterpenes - pharmacology; X-ray diffraction
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2017.01.007

Eleven highly halogenated chamigrane sesquiterpenoids, compositacins A–K, including one unusual rearranged chamigrane sesquiterpenoid, compositacin A, were isolated from the red alga Laurencia composita Yamada, along with seven known structural analogues. Compositacins B and D are the first examples of chamigranes bearing an ether bridge involving C-5/C-9 and C-3/C-5, respectively, while compositacins B and C represent the first chamigranes with a C-10 carbonyl group. Their structures were elucidated on the basis of extensive spectroscopic analysis. The absolute configuration of compositacin B was determined by ECD calculation, whereas the absolute configurations of compositacins A and C–L were proposed on biosynthetic grounds by comparison to compositacin B and the related known sesquiterpenoids johnstonol and yicterpene A. We also suggest that the structure of the previously reported sesquiterpenoid laurokamin A should be revised. Cytotoxicity and antifungal activity of these isolates were also investigated. The results showed that compositacin G exhibited good antifungal activity against Microsporum gypseum (Cmccfmza) with a MIC80 value of 4 μg/mL relative to positive controls. Four of the chamigrane halosesquiterpenoids showed marginal cytotoxicity against the A-549 human lung adenocarcinoma cell line with IC50 values ranging from 48.6 to 85.2 μM. [Display omitted] •Eleven highly halogenated chamigrane sesquiterpenoids were isolated from Laurencia composita.•Compositacins B and D are the first examples of chamigranes bearing novel ether bridges.•Compositacins B and C represent the first chamigranes containing a C-10 carbonyl group.•Some isolates exhibited moderate antifungal activity against eight fungi.•Four of eighteen compounds showed marginal cytotoxicity against two human cancer cell lines.