Arizona State University

Arizona Board of Regents, a Body Corporate

Matthew P Grealish

George R Pettit

Described herein are novel compounds having antineoplastic and antimicrobial activity, obtained via structural modifications of resveratrol and combretastatin A-4, methods for synthesis of these compounds, and their use in pharmaceutical composition and for use in the treatment of mammals having cancer. Examples of the novel compounds are: (Z)- and (E)-3,4',5-trimethoxystilbene (4a, 4b); (Z)- and (E)-3,5-dimethoxy-4&#x2032;-hydroxystilbene (14c, 14d); (Z)- and (E)-3-hydroxy-4&#x2032;,5-dimethoxystilbene (14g, 14h); (Z)- and (E)-3,5-dihydroxy-4&#x2032;-methoxy-stilbene (14k, 14l); sodium resverastatin dibenzyl phosphate ((Z)-3,5-dimethoxy-4-[O-bis(benzyl)phosphoryl]-stilbene) (14m); and sodium resverastatin phosphate (14n).

Structural modification of resveratrol: sodium resverastatin phosphate

The benzophenone derivative of combretastatin A-1, designated &ldquo;hydroxyphenstatin&rdquo;, was synthesized by compiling a protected bromobenzene and a benzaldehyde to form a benzhydrol which was subsequently oxidized to the ketone. Hydroxyphenstatin was converted to a sodium phosphate prodrug by dibenzyl phosphite phosphorylation and subsequent benzyl cleavage: Hydroxyphenstatin and the prodrugs thereof were found to be a potent inhibitor of tubulin polymerization and to demonstrate surprisingly effective antineoplastic activity against a series of human cancer cells and murine P388 lymphocytic leukemia cells.

Growing community of inventors

San Diego, CA, United States of America

Matthew P Grealish