New lead synthetic compounds with chemical structures which heretofore were not known to be tubulin active were identified using the Compare pattern-recognition algorithm. The database of responses by cell lines used in the NCI in vitro screen to all the synthetic and natural product compounds screened at a given time was probed with a set of the most potent tubulin-active compounds known. Compounds selected by the computer algorithm were evaluated by Dr. E. Hamel as inhibitors of in vitro tubulin polymerization and for their ability to cause mitotic arrest of cells grown in culture. A class of nitrobenzoylureas, which were not previously known to have tubulin activity, were among the new chemical classes identified to be potent inhibitors of tubulin polymerization and were established to cause mitotic arrest of HL-60 cells. Studies directed towards a potential clinical candidate are in progress.
