Isolation and structure of pedilstatin from a republic of maldives Pedilanthus sp.

Abstract

A new cancer cell growth inhibitor designated pedilstatin (1) was isolated from a Republic of Maldives Pedilanthus sp. The structure was determined to be 13-O-acetyl-12-O-[2'Z,4'E-octadienoyl]-4alpha-deoxyphorbol on the basis of high-resolution mass spectral and 2D NMR assignments. Pedilstatin was found to significantly inhibit growth of the P388 lymphocytic leukemia cell line with an ED(50) of 0.28 microg/mL, to afford, at concentrations of 2-5 microM, protection (to 80%) of human-derived lymphoblastoid CEM-SS cells from infection and cell-killing by HIV-1, and to show inhibition of protein kinase C with a K(i) of 620 +/- 20 nM.

• Authors: George R Pettit, Sylvie Ducki, Rui Tan, Roberta S Gardella, James B McMahon, Michael R Boyd, George R Pettit 3rd, Peter M Blumberg, Nancy E Lewin, Dennis L Doubek, Larry P Tackett, Michael D Williams
• Journal: Journal of natural products (J Nat Prod) Vol. 65 Issue 9 Pg. 1262-5 (Sep 2002) ISSN: 0163-3864 [Print] United States
• PMID: 12350143 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents, Phytogenic
• Antiviral Agents
• Enzyme Inhibitors
• Phorbols
• pedilstatin
• Protein Kinase C

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Antiviral Agents (chemistry, isolation & purification, pharmacology)
• Cell Survival (drug effects)
• Enzyme Inhibitors (chemistry, isolation & purification, pharmacology)
• Euphorbiaceae (chemistry)
• HIV-1 (metabolism)
• Humans
• Indian Ocean Islands
• Leukemia P388
• Lymphocytes (drug effects)
• Mice
• Molecular Structure
• Phorbols (chemistry, isolation & purification, pharmacology)
• Plants, Medicinal (chemistry)
• Protein Kinase C (antagonists & inhibitors)
• Structure-Activity Relationship
• Tumor Cells, Cultured (drug effects)