Identification of 2-benzimidazolyl urea as a new antimitotic compound based on cross resistance studies with nocodazole resistance mutants of CHO cells.

The cross resistance patterns of a set of nocodazole-resistant (NocR) and podophyllotoxin-resistant (PodR) mutants of Chinese hamster ovary cells, which exhibit highly specific cross resistance towards compounds that show nocodazole-like antimitotic activity, towards a large number of benzimidazole derivatives have been examined. Of the various compounds examined, the NocR and the PodR mutants were found to exhibit increased cross resistance towards only 2-benzimidazolyl urea, indicating that this compound may possess similar biological activity as nocodazole. The nocodazole-like antimitotic activity of 2-benzimidazolyl urea has been confirmed by its ability to block cells in mitosis, and by its competition of 3H-podophyllotoxin binding to microtubule proteins in cell extracts. The nocodazole-like behavior of 2-benzimidazolyl urea and lack of similar activity in other benzimidazole derivatives examined, provides valuable information regarding structural features that are required for this type of biological activity.