Antineoplastic agents. 529. Isolation and structure of nootkastatins 1 and 2 from the Alaskan yellow cedar Chamaecyparis nootkatensis.
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.
Pettit
George R
GR
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-2404, USA. bpettit@asu.edu
Tan
Rui
R
Northen
Julian S
JS
Herald
Delbert L
DL
Chapuis
Jean-Charles
JC
Pettit
Robin K
RK
D000413:Alaska; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D029780:Chamaecyparis / Q000737:chemistry*; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005658:Fungi / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D007941:Leukemia P388; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010946:Plants, Medicinal / Q000737:chemistry*; D014197:Trees / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; C493070:nootkastatin 1; C493071:nootkastatin 2