Antineoplastic Agents. 536. New Sources of Naturally Occurring Cancer Cell Growth Inhibitors from Marine Organisms, Terrestrial Plants, and Microorganisms 1a , ⊥ George R. Pettit,* ,† Fiona Hogan, † Jun-Ping Xu, † Rui Tan, † Toshihiko Nogawa, † Zbigniew Cichacz, † Robin K. Pettit, † Jiang Du, † Qing-Hua Ye, † Gordon M. Cragg, ‡ Cherry L. Herald, † Michael S. Hoard, † Animesh Goswami, † Justin Searcy, † Larry Tackett, † Dennis L. Doubek, † Lee Williams, † John N. A. Hooper, § Jean M. Schmidt, † Jean-Charles Chapuis, † Denise N. Tackett, † and Felicia Craciunescu † Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State UniVersity, P.O. Box 872404, Tempe, Arizona 85287-2404, Natural Products Branch, DeVelopmental Therapeutics Program, DiVision of Cancer Treatment and Diagnosis, National Cancer Institute, P.O. Box B, Frederick, Maryland 21702-1201, and Queensland Museum, P.O. Box 3300, S. Brisbane, Queensland, 4101 Australia ReceiVed December 21, 2007 Bioassay-guided fractionation of extracts of various plants, marine organisms, and microorganisms has led to the discovery of new natural sources of a number of known compounds that have significant biological activity. The isolation of interesting and valuable cancer cell growth inhibitors including majusculamide C (1), axinastatin 5 (5), bengazoles A (6), B (7), and E (8), manzamine A (10), jaspamide (11), and neoechinulin A (19) has been summarized. As an inevitable result of our long-term and broad research program directed at discovery of new anticancer drugs from plants, marine organisms, and microorganisms, we continue to isolate constituents that show significant activity in our murine leukemia and human cancer cell lines and that prove to be known substances. The following is a report of such previously discovered compounds that have been isolated in our laboratories and would not otherwise be described in our literature record. New sources of many of these compounds are reported here. The information may lead to greater availability of some promising anticancer drug candidates and may also help other research groups to avoid pursuing natural product leads that have already been investigated for their anticancer constituents. Table 1 lists these compounds and the species from which they were newly extracted as well as the organisms from which they were previously isolated. Many of the known com- pounds already had biological activity ascribed to them, but fewer had been reported to have cancer cell growth inhibitory activity or had been tested against the cell lines that we use (Table 2). Results and Discussion Plant and animal samples were preserved for shipment from the collection site in CH 3 OH, CH 2 Cl 2 –CH 3 OH, or C 2 H 5 OH. Upon arrival in our laboratories, the shipping solution was decanted, concentrated, and extracted with CH 2 Cl 2 . Unless otherwise de- scribed in the individual entries, the residual sample material was extracted with a 1:1 mixture of CH 2 Cl 2 -CH 3 OH, to which was added water in order to effect separation of the phases, and the CH 2 Cl 2 layer was removed and added to the initial CH 2 Cl 2 extract. The combined CH 2 Cl 2 solution was dried and the residue dissolved in a 9:1 mixture of CH 3 OH–H 2 O. Following extraction with hexane, the aqueous layer was adjusted to 3:2 CH 3 OH–H 2 O and extracted with CH 2 Cl 2 . The CH 3 OH–H 2 O, hexane, and CH 2 Cl 2 layers were each dried, and the residues were evaluated for anticancer activity. Fungal and bacterial broths were initially extracted with either ethyl acetate or CH 2 Cl 2 , and the extract was dried to give a residue that was taken up in 9:1 CH 3 OH–H 2 O and partitioned according to the above method 1b to yield residues that were similarly tested for activity. Extracts that showed activity were subjected to a series of chromatographic separations on columns of Sephadex LH-20 in suitable solvent systems such as CH 3 OH, hexane–toluene–CH 3 OH (3:1:1), and toluene–CH 3 OH–2-propanol (8:1:1); final purification of the active compounds was performed by HPLC. Now follows a summary of the most promising cell growth inhibitors that we ⊥ Dedicated to Dr. G. Robert Pettit of Arizona State University for his pioneering work on bioactive natural products. * To whom correspondence should be addressed. Tel: (480) 965-3351. Fax: (480) 965-2747. E-mail: bpettit@asu.edu. † Arizona State University. ‡ National Cancer Institute, Frederick. § Queensland Museum. J. Nat. Prod. 2008, 71, 438–444 438 10.1021/np700738k CCC: $40.75  2008 American Chemical Society and American Society of Pharmacognosy Published on Web 03/08/2008