Palmadorin chemodiversity from the Antarctic nudibranch Austrodoris kerguelenensis and inhibition of Jak2/STAT5-dependent HEL leukemia cells |
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| Authors: | J Alan Maschek Emily Mevers Thushara Diyabalanage Liwei Chen Yuan Ren James B McClintock Charles D Amsler Jie Wu Bill J Baker |
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| Institution: | 1. Department of Chemistry, University of South Florida, Tampa, FL 33620, USA;2. Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA;3. Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;4. Center for Drug Discovery and Innovation, University of South Florida, Tampa, FL 33620, USA |
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| Abstract: | Detailed investigation of the Antarctic nudibranch Austrodoris kerguelenensis has resulted in the isolation of a diverse suite of new diterpenoid glyceride esters (1–16) related to the palmadorins (17–19), including one (palmadorin L (9)) that is the first halogenated diterpene from this well-studied nudibranch. Previous collections of A. kerguelenensis from McMurdo Sound, the Weddell Sea and the Western Antarctic Peninsula have afforded related diterpene glycerides, a natural product class implicated as a chemical defense in nudibranchs. In this paper we describe the isolation, structure elucidation, and stereochemical analysis of sixteen new palmadorins using a combination of one- and two-dimensional NMR techniques. Palmadorin A (17), B (18), D (1), M (10), N (11), and O (12) inhibit human erythroleukemia (HEL) cells with low micromolar IC50's, and palmadorin M inhibits Jak2, STAT5, and Erk1/2 activation in HEL cells and causes apoptosis, at 5 μM. |
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