Effects of benzimidazoles on mouse and rat limb bud cells in culture.

Benzimidazoles exhibited an inhibitory action on the chondrogenesis in a mouse limb bud cell culture system; further, nitro and chloro groups at the 5 position in 2-(2-pyridyl)benzimidazole were found to be potent substituents. However, 2-(2-pyridyl)benzoxazole and 5-methoxy-2-(2-pyridyl)benzothiazole exhibited no inhibitory action under our experimental conditions. Thus, imidazole NH proton seemed to be important in the inhibitory action in the mouse cell system. The concentrations of thiabendazole (TBZ), 5-hydroxy-TBZ (5-HY-TBZ) and N-methyl-TBZ necessary to reduce the amounts of cartilage proteoglycan by 50% (TP50) were estimated to be about 0.35, 0.25 and 0.70 mM, respectively, in the rat limb bud cell culture system. The TP50 of TBZ and 5-HY-TBZ in the rat cell system were 3- to 4-fold higher than those in the mouse cell system.