We report the effects of indenestrol A, a metabolite of diethylstilbestrol, and its analogue, indenestrol B, on the relative plating efficiency and cellular microtubular architecture of Chinese hamster V79 cells. In this study, the effects of the monomethyl ethers of indenestrols A and B on these biological activities and their affinity for estrogen receptors in cytosol from mouse uteri were investigated. The results indicate that among eight optically active and four racemic methyl ethers, the 4′-methyl ether of [(-)-3S] indenestrol B exhibits both the strongest cytotoxicity in, and greatest disruption of, the cellular microtubular architecture of Chinese hamster V79 cells in culture. For the 6-and 4′-monomethyl ethers of optically active indenestrols A and B, some correlation was found between cytotoxicity and the effect on the distribution of cellular microtubular networks in Chinese hamster V79 cells. Estrogen receptor competitive binding studies revealed that stereochemistry and the position (6 or 4′) of the methyl ether group contributed greatly to their binding affinity. However, no correlation was observed between the affinity for estrogen receptors and the cytotoxicity of the monomethyl ethers tested. This suggests that the important causes of cytotoxicity in this series of compounds involve the inhibitory activity on cellular microtubule networks and not the affinity for estrogen receptors.
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