Combretastatin A-4

• US 4,996,237 A
• Filed: 02/22/1988
• Issued: 02/26/1991
• Est. Priority Date: 01/06/1987
• Status: Expired due to Term

• Current Assignee: Arizona Board of Regents (University of Arizona)
• Original Assignee: Arizona Board of Regents (University of Arizona)
• Inventors: Pettit, George R., Singh, Sheo B.
• Primary Examiner(s): Rollins, John W.
• Application Number:
  US07/158,866
• Time in Patent Office: 1,100 Days
• Field of Search: 568/631, 568/646, 514/720, 514/721
• US Class Current: 514/720
• CPC Class Codes: C07C 43/23 containing hydroxy or O-metal groups
• CPC Class Codes: C07D 317/64 Oxygen atoms

Abstract

The African tree Combretum caffrum (Combretaceae) has been found to contain an agent which is a powerful inhibitor of tubulin polymerization (IC50 2-3 μM), the growth of murine lymphocytic leukemia (L1210 and P388 with ED50 <0.003 mg/ml and human colon cancer cell lines (e.g. VoLo with ED50 <0.01 μg/ml). This agent is herein denominated "combretastatin A-4". The structure assigned by spectral techniques was confirmed by synthesis.

Claims

1. A compound denominated combretastatin A-4 and for inhibiting tubulin polymerization having the structural formula:

##STR2##

2. A pharmaceutical preparation containing a pharmacologically acceptable carrier and, as its essential active ingredient, a compound denominated combretastatin A-4 having the structural formula:

##STR3##

3. A method of treating a host afflicted with a neoplastic disease selected from the group consisting of lymphocytic leukemia and human colon cancer comprising administering to said host a cell-growth inhibitory amount of a natural or synthetic substance denominated combretastatin A-4 or a pharmaceutically active non-toxic derivative thereof in a pharmaceutically acceptable carrier, said substance having the structural formula:

##STR4##