Isolation and Structure of Pedilstatin from a Republic of Maldives Pedilanthus sp

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2002-09, Vol.65 (9), p.1262-1265
• Main Authors: Pettit, George R, Ducki, Sylvie, Tan, Rui, Gardella, Roberta S, McMahon, James B, Boyd, Michael R, Blumberg, Peter M, Lewin, Nancy E, Doubek, Dennis L, Tackett, Larry P, Williams, Michael D
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Antiviral Agents - chemistry; Antiviral Agents - isolation & purification; Antiviral Agents - pharmacology; Cell Survival - drug effects; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Euphorbiaceae - chemistry; HIV-1 - metabolism; Humans; Indian Ocean Islands; Leukemia P388; Lymphocytes - drug effects; Mice; Molecular Structure; Phorbols - chemistry; Phorbols - isolation & purification; Phorbols - pharmacology; Plants, Medicinal - chemistry; Protein Kinase C - antagonists & inhibitors; Structure-Activity Relationship; Tumor Cells, Cultured - drug effects
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np020115b

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]-4α-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 ED50 of 0.28 μg/mL, to afford, at concentrations of 2−5 μM, 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.