Diaryl disulfides and diaryl thiosulfonates were synthesized with the two phenyl rings of all compounds bearing identical halide substituents. Because of structural similarity to the potent antimitotic natural product combretastatin A-4 (CA-4), the compounds were examined for inhibition of tubulin polymerization, and the thiosulfonates were more active than the disulfides. The nine thiosulfonates had IC₅₀ values ranging from 1.2 to 9.1 µM, as compared with 1.3 µM obtained with CA-4. The compounds thus ranged from equipotent with CA-4 to 7-fold less active. The nine disulfides had IC₅₀ values ranging from 1.2 to 5.1 µM, as compared with 0.54 µM obtained with CA-4. The compounds thus ranged from less than half as active as CA-4 to over 9-fold less active. The most active members of each group, 2 g and 3c, in the assembly assay were modeled into the colchicine site. Compound 3c had significant hydrophobic interactions with β-tubulin residues CYS 241 and ALA 250, and its thiosulfonate bridge made a hydrogen bond with β-tubulin residue ASN 258. Compound 2 g had hydrophobic interactions with β-tubulin residues ALA 250, CYS 241 and ALA 254, but there was no significant interaction of the disulfide bridge with tubulin.

合成二芳基二硫化物和二芳基硫代磺酸盐，所有化合物的两个苯环都带有相同的卤化物取代基。由于与有效的抗有丝分裂天然产物 Combretastatin A-4 (CA-4) 的结构相似，因此检查了这些化合物对微管蛋白聚合的抑制作用，并且硫代磺酸盐比二硫化物更具活性。九种硫代磺酸盐的 IC ₅₀值为 1.2 至 9.1 µM，而 CA-4 的 IC 50 值为 1.3 µM。因此，化合物的范围从与 CA-4 等效到活性低 7 倍不等。九个二硫化物的 IC ₅₀值范围为 1.2 至 5.1 µM，而 CA-4 获得的值为 0.54 µM。因此，这些化合物的活性范围从不到 CA-4 的一半到活性低 9 倍以上。在组装测定中，每组中最活跃的成员2 g和3c被建模到秋水仙碱位点。化合物3c与 β-微管蛋白残基 CYS 241 和 ALA 250 具有显着的疏水相互作用，其硫代磺酸盐桥与 β-微管蛋白残基 ASN 258 形成氢键。化合物2g与 β-微管蛋白残基 ALA 250、CYS 241 和ALA 254，但二硫键与微管蛋白没有显着的相互作用。