ANTIMITOTIC ACTIVITY OF DIARYL COMPOUNDS WITH STRUCTURAL FEATURES RESEMBLING COMBRETASTATIN A-4

Series of diaryl ethers, amines and amides have been synthesized and t ested for antitumor activity. These diaryl compounds possess some of t he structural features of combretastatin A-4 (a potent antimitotic age nt). They were designed to discover whether transferring these structu ral motifs from stilbenes to heterosubstituted diaryl compounds would enhance their biochemical activities. Molecular modeling studies sugge sted that these diaryl compounds could adopt conformations similar to combretastatin A-4. However, although some agents (5-7) were cytotoxic and others (10 and 12) could interact with tubulin, none were as pote nt as combretastatin A-4. [(C) 1998 Lippincott-Raven Publishers.].