66938-94-1Relevant articles and documents
Synthesis, Tubulin Binding, Antineoplastic Evalutaion, and Structure-Activity Relationship of Oncodazole Analogues
Kruse, Lawrence I.,Ladd, David L.,Harrsch, Peter B.,McCabe, Francis L.,Mong, Shau-Ming,et al.
, p. 409 - 417 (2007/10/02)
n an attempt to identify a soluble oncodazole analogue that could be easily formulated, a series of substituted oncodazoles was synthesized and evaluated for tubulin binding affinity, in vitro cyctotoxicity against cultured mouse B-16 cells, and ability to prolong lifespan at the maximally tolerated dose in the P388 mouse leukemia model.Biological evaluation of all the isomeric methyloncodazoles demonstrated the thiophene 4'-position to be the only site of significant bulk tolerance, although substitution of this position with polar or charged functional groups abolished biological activity.Simple esters of the 4'-carboxymethyloncodazole were shown to have enhanched antitumor activity and tubulin binding affinity relative to oncodazole.Despite a failure of this study to identify a water-soluble oncodazole with antitumor activity, the structure-activity relationship developed led to a derivative with enhanced activity in the P388 leukemia model and facilitated the preparation of a biologically active photolabile analogue.
