Antineoplastic agents. 529. Isolation and structure of nootkastatins 1 and 2 from the Alaskan yellow cedar Chamaecyparis nootkatensis.

Abstract

The yellow cedar tree, Chamaecyparis nootkatensis, collected in southeast Alaska was evaluated as a potential source of new anticancer agents. Two new diterpene anticancer constituents termed nootkastatins 1 (4) and 2 (5) were isolated along with three previously known diterpene cancer cell growth inhibitors where two were reported as synthetic modifications of totarol and not previously found in nature. All five diterpene structures were established by HRMS and 1D and 2D NMR spectroscopic analyses combined with three X-ray crystal structure determinations (2, 3, and 5). Against a panel of six human cancer cell lines, this series of diterpenes exhibited inhibition over the range GI(50) 0.75-2.0 microg/mL, and all inhibited the growth of Gram-positive bacteria and fungi.

• Authors: George R Pettit, Rui Tan, Julian S Northen, Delbert L Herald, Jean-Charles Chapuis, Robin K Pettit
• Journal: Journal of natural products (J Nat Prod) Vol. 67 Issue 9 Pg. 1476-82 (Sep 2004) ISSN: 0163-3864 [Print] United States
• PMID: 15387645 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents, Phytogenic
• Diterpenes
• nootkastatin 1
• nootkastatin 2

Topics

• Alaska
• Animals
• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Chamaecyparis (chemistry)
• Diterpenes (chemistry, isolation & purification, pharmacology)
• Drug Screening Assays, Antitumor
• Fungi (drug effects)
• Gram-Positive Bacteria (drug effects)
• Humans
• Leukemia P388
• Mice
• Molecular Structure
• Nuclear Magnetic Resonance, Biomolecular
• Plants, Medicinal (chemistry)
• Trees (chemistry)
• Tumor Cells, Cultured