Lluis MIR , Marie - Louise OUSTRIN , Pierre LECOINTE and Michel
نویسنده
چکیده
Griseofulvin, an antifungic metabolite produced by several species of Penicillium [ 1 ] , is widely used in human and animal therapy [2]. Its mechanism of action remained puzzling for along time [3]. Recently it has been shown that griseofulvin inhibits the polymerization of purified brain tubulin [4,5]. Although this property may account for its in vivo effects, this result does not allow to rule out the hypothesis that microtubule proteins may not be the main target of this drug [6]. In order to check this possibility, several griseofulvin derivatives exhibiting a lower or a higher activity than griseofulvin, were synthesized. Their in vivo effects were studied on a mouse leukemia cell line (L1210) and on a Myxomycete (Physarum). Their in vitro action was studied by monitoring the induced aggregation and the inhibition of polymerization of purified brain mammalian microtubule proteins [4,5]. It was found that the in vitro activities of the various griseofulvin derivatives were in correlation with their in vivo activities suggesting that microtubule proteins do represent the pharmacological target ofgriseofulvin.
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