Stereochemical Studies of the Karlotoxin Class Using NMR Spectroscopy and DP4 Chemical‐Shift Analysis: Insights into their Mechanism of Action
| Autor: | Mark T. Hamann, Amanda L. Waters, Joonseok Oh, Allen R. Place |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Angewandte Chemie. 127:15931-15936 |
| ISSN: | 1521-3757 0044-8249 |
| Popis: | After publication of karlotoxin 2 (KmTx2; 1), the harmful algal bloom dinoflagellate Karlodinium sp. was collected and scrutinized to identify additional biologically active complex polyketides. The structure of 1 was validated and revised at C49 using computational NMR tools including J-based configurational analysis and chemical-shift calculations. The characterization of two new compounds [KmTx8 (2) and KmTx9 (3)] was achieved through overlaid 2D HSQC NMR techniques, while the relative configurations were determined by comparison to 1 and computational chemical-shift calculations. The detailed evaluation of 2 using the NCI-60 cell lines, NMR binding studies, and an assessment of the literature supports a mode of action (MoA) for targeting cancer-cell membranes, especially of cytostatic tumors. This MoA is uniquely different from that of current agents employed in the control of cancers for which 2 shows sensitivity. |
| Databáze: | OpenAIRE |
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