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.
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D005260:Female; D007700:Kinetics; D008938:Mitosis / Q000187:drug effects; D009154:Mutation; D015739:Nocodazole; D010053:Ovary; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000633:toxicity
D001562:Benzimidazoles; C051850:2-benzimidazolylurea; D014508:Urea; D015739:Nocodazole