Lamellarin Sulfates from the Pacific Tunicate Didemnum ternerratum

• Published in: Journal of natural products (Washington, D.C.) Vol. 82; no. 7; pp. 2000 - 2008
• Main Authors: Bracegirdle, Joe, Robertson, Luke P, Hume, Paul A, Page, Michael J, Sharrock, Abigail V, Ackerley, David F, Carroll, Anthony R, Keyzers, Robert A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 26.07.2019; Amer Chemical Soc
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Chemistry, Medicinal; Colonic Neoplasms - drug therapy; Coumarins - chemistry; Coumarins - isolation & purification; Coumarins - pharmacology; Heterocyclic Compounds, 4 or More Rings - chemistry; Heterocyclic Compounds, 4 or More Rings - isolation & purification; Heterocyclic Compounds, 4 or More Rings - pharmacology; Humans; Inhibitory Concentration 50; Isoquinolines - chemical synthesis; Isoquinolines - chemistry; Isoquinolines - isolation & purification; Isoquinolines - pharmacology; Life Sciences & Biomedicine; Mass Spectrometry - methods; Pharmacology & Pharmacy; Plant Sciences; Science & Technology; ELECTRONIC CIRCULAR-DICHROISM; ASSIGNMENT; NATURAL-PRODUCTS; THERMOCHEMISTRY; ALKALOIDS
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.9b00493

Six new lamellarin sulfates (1–6) were isolated from the methanolic extract of the Pacific tunicate Didemnum ternerratum, collected from the Kingdom of Tonga. Mass spectrometric molecular networking through the GNPS platform was used to target the isolation of 1–6. Planar structures were elucidated through a combination of NMR and MS experiments. Through comparison of experimental and calculated ECD spectra, the absolute configurations of atropisomers 2–5 were determined, with their energetic barriers to racemization also determined computationally. The cytotoxicity of the compounds was tested against the human colon carcinoma cell line HCT-116, where lamellarin D-8-sulfate (5) exhibited moderate activity with an IC50 of 9.7 μM.