Antineoplastic Agents 385. The Isolation and Structure of a Scalarane-Type Sesterterpene from the Indian Ocean Porifera Hyrtios erecta

1998 ◽  
Vol 63 (10) ◽  
pp. 1671-1677 ◽  
Author(s):  
George R. Pettit ◽  
Zbigniew A. Cichacz ◽  
Rui Tan ◽  
Delbert L. Herald ◽  
Noeleen Melody ◽  
...  

Bioassay-guided separation techniques were employed to isolate (3.3·10-7% yield) a new murine P388 lymphocytic leukemia cell line inhibitor (ED50 2.9 μg/ml) 12-O-deacetyl-19-deoxyscalarin from extracts of the Republic of Maldives marine sponge Hyrtios erecta. The structure was deduced using high field 2D NMR and high resolution mass spectral methods and confirmed by X-ray crystal structure determination.

1992 ◽  
Vol 70 (4) ◽  
pp. 1170-1175 ◽  
Author(s):  
George R. Pettit ◽  
Jeremiah C. Collins ◽  
Delbert L. Herald ◽  
Dennis L. Doubek ◽  
Michael R. Boyd ◽  
...  

The blue marine sponge cribrostatins 1 (1, 8.8 × 10−6% yield) and 2 (2, 3.1 × 10−6% yield) active against the P388 lymphocytic leukemia cell line (ED50 1.58 and 2.73 μg/mL respectively) have been isolated. The previously known isoquinolinequinones mimosamycin (3), renierone (4), and O-demethylrenierone (5) were also isolated and shown to display activity against the P388 cell line (ED50 0.73, 2.75, and 8.36 μg/mL, respectively). Importantly, both cribrostatin 1 and mimosamycin showed selective activity against all of the nine human melanoma cell lines employed by the U.S. National Cancer Institute. Structural determinations were accomplished utilizing high field nuclear magnetic resonance (400 MHz) and mass spectral studies. Confirmation of the cribrostatin 1 structure was achieved by X-ray crystallographic techniques.


1988 ◽  
Vol 66 (3) ◽  
pp. 406-413 ◽  
Author(s):  
George R. Pettit ◽  
Sheo Bux Singh ◽  
Margaret L. Niven ◽  
Jean M. Schmidt

Combretum caffrum, a tree in the family Combretaceae, has been found to contain three 9,10-dihydrophenanthrenes (6,7-dihydroxy-2,3,4-trimethoxy; 7-hydroxy-2,3,4,6-tetramethoxy; and 2,7-dihydroxy-3,4,6-trimethoxy) that inhibit (ED50 2.2, 2.8, and 2.6 μg/mL) growth of the murine lymphocytic leukemia cell line. One phenanthrene (7-hydroxy-2,3,4,6-tetramethoxy) was also isolated with similar (ED50 2.0 μg/mL) activity. Structures for each of these substances, including a dihydrophenanthrene (2-hydroxy-3,4,6,7-tetramethoxy-9,10-dihydrophenanthrene), were determined by detailed high resolution nuclear magnetic resonance and mass spectral studies and (or) X-ray crystal structure analysis.


Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 234-243 ◽  
Author(s):  
Lindsey J. White ◽  
Bradford W. Ozanne ◽  
Pierre Graber ◽  
Jean-Pierre Aubry ◽  
Jean-Yves Bonnefoy ◽  
...  

Abstract Human CD23 is a 45-kD type II membrane glycoprotein, which functions as a low-affinity receptor for IgE and as a ligand for the CD21 and CD11b/CD11c differentiation antigens. CD23 is released from the surface of cells as soluble fragments, and a 25-kD species of soluble CD23 (sCD23) appears to act as a multifunctional cytokine. In this report, sCD23 is shown to sustain the growth of low cell density cultures of a human pre-B–acute lymphocytic leukemia cell line, SMS-SB: no other cytokine tested was able to induce this effect. Flow cytometric analysis indicates that sCD23 acts to prevent apoptosis of SMS-SB cells. SMS-SB cells cultured at low cell density possess low levels of bcl-2 protein. Addition of sCD23 to cells at low cell density maintained bcl-2 expression at levels equivalent to those observed in SMS-SB cells cultured at higher cell densities. No CD23 mRNA was found in SMS-SB cells, ruling out an autocrine function for CD23 in this cell line model. Although SMS-SB cells do not express the known receptors for CD23, namely CD21, CD11b-CD18, or CD11c-CD18, the cells specifically bind CD23-containing liposomes, but not glycophorin-containing liposomes. Binding of CD23-containing liposomes is inhibited by anti-CD23 but not by anti-CD21 or anti-CD11b/c monoclonal antibodies. The data show that sCD23 prevents apoptosis of the SMS-SB cell line by acting through a novel receptor.


1990 ◽  
Vol 84 (3) ◽  
pp. 156-161 ◽  
Author(s):  
Hiromitsu Matsuzaki ◽  
Hiroyuki Hata ◽  
Norio Asou ◽  
Hitoshi Suzushima ◽  
Yoshitaka Akahoshi ◽  
...  

2014 ◽  
Vol 68 (2) ◽  
Author(s):  
Marco Persico ◽  
Patrizia Chiari ◽  
Raffaela Biesuz ◽  
Giancarla Alberti

AbstractCurrent cancer treatments lead to insufficient distribution of therapeutic agents in tumor cells due to their lack of selectivity often causing adverse effects in the normal cell uptake of the drug. The challenge is to design therapeutic drugs able to maximize the treatment of malignant cancers while minimizing their adverse effects. In this study, 10B incorporation in the B chronic lymphocytic leukemia cell line MEC-1 was investigated. The cells were treated with l-p-10borophenylalanine (10BPA) and 10boron immuno-nanoparticles (BNPs) loaded with 10BPA with or without the anti-CD20 monoclonal antibody for different contact times. The uptake of 10B by the cells was determined by the inductively coupled plasma mass spectrometry (ICP-MS) after acid mineralization. To obtain accurate and consistent data, the analytical procedure was optimized using factorial experimental design. It was observed that BNP loaded with 10BPA and anti-CD20 represents the best carrier system for 10B in B cells for long time (>10 h) whereas 10BPA seems to be the top drug for short time (< 4 h) procedures.


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