Abstract
A series of A-ring polymethoxylated neoflavonoids was prepared by ligand coupling reactions involving either Suzuki or Stille reactions. Cytotoxicity studies indicated a potent activity against a CEM leukemia cell line for the compounds presenting a substitution pattern related to that of combretastatin A-4. The two compounds having a 3'-OH and a 4'-OCH(3) substituents on the 4-phenyl B-ring have no effect on human topoisomerases I and II but potently inhibit, in vitro, microtubule assembly. At the cell level, the active compounds were characterized as proapoptotic agents, but they can also trigger cell death via a nonapoptotic pathway.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemical synthesis*
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology
-
Apoptosis / drug effects
-
Biopolymers
-
Caspases / metabolism
-
Cell Cycle / drug effects
-
Cell Line, Tumor
-
DNA Topoisomerases, Type I / chemistry
-
DNA Topoisomerases, Type II / chemistry
-
Drug Screening Assays, Antitumor
-
Enzyme Activation
-
Flow Cytometry
-
Humans
-
Membrane Potentials / drug effects
-
Mitochondria / drug effects
-
Mitochondria / physiology
-
Stilbenes / chemical synthesis*
-
Stilbenes / chemistry
-
Stilbenes / pharmacology
-
Structure-Activity Relationship
-
Topoisomerase I Inhibitors
-
Topoisomerase II Inhibitors
-
Tubulin / chemistry
Substances
-
Antineoplastic Agents
-
Biopolymers
-
Stilbenes
-
Topoisomerase I Inhibitors
-
Topoisomerase II Inhibitors
-
Tubulin
-
Caspases
-
DNA Topoisomerases, Type I
-
DNA Topoisomerases, Type II
-
fosbretabulin