The synthesis and biological evaluation is presented for a new class of tubulin-targeting agents, termed "combretatropones," that incorporate the 1,2-diaryl ethane nucleus of combretastatin and the tropone moiety of colchicine. The tubulin-microtubule system is the target for a large number of drugs which possess a wide range of therapeutic utilities. These drugs include colchicine 1, combretastatin 2, the vinca alkaloids, maytansine and taxol. Although over 200 analogs of colchicine have been prepared, most have been derived through semisynthetic modification of the parent and, thus, limited in the scope of fundamental molecular alterations. Nonetheless, these analogs have enabled an understanding of the structure-activity relationships for the colchicinoid system, provided a potential avenue for the exploitation of tubulin isotypes in therapy, and assisted in the elucidation of the colchicine binding site on tubulin. Combretastatin has also been shown to associate with the "colchicine binding site" on tubulin. In our design of the "combretatropones", several observations derived from the structure-activity evaluations of the combretastatin and colchicine nuclei were utilized. These are summarized as follows: 1. The bis-aryl ring system is critical. The two aryl rings can be directly linked (i.e., colchicine 1) or linked via a "bridging carbon spacer", such as a methylene unit (i.e., podophyllotoxin) or a 1,2 disubstituted ethyl unit (i.e, combretastatin 2). The bis-aryl system can consist of two aromatic rings (i.e., combretastatin 2) or an aromatic ring and a tropone ring (i.e., colchicine 1). Maximum activity has been observed when a trimethoxy phenyl ring of the appropriate regiochemistry is present. The nature and regiochemistry of the substituents present on the tropone ring are significant. Combretatropones 3 and 4 incorporate the 1,2-diaryl ethane nucleus of combretastatin and the tropone moiety of colchicine in a fashion consistent with the detailed structure-activity relationships. Figures 4 and 5 illustrate the superimposition of combretatropone 3 with colchicine 1 and combretastatin 2. Figure 4 illustrates the geometric proximity, but not equivalence, of the aryl substituents in 3 to those found in colchicine 1. Figure 5 illustrates the geometric equivalence of the functional groups in combretatropone 3 to those in combretastatin 2. Thus, analysis by molecular modelling of the combretatropone system predicts that 3 and 4 should exhibit SAR behavior more "combretastatin-like" than "colchicine-like" in their interactions with tubulin.