The computer-automated structure evaluation programs MultiCASE and CASE were used to perform a quantitative structure-activity relationship study on tubulin polymerization inhibitors. A learning set of 536 chemicals (202 active. 27 marginal, and 307 inactive), built using IC50 values for inhibition of tubulin polymerization or mitosis from this and previous studies, was used for artificial inte...

These studies explore the effects of an epipodophyllotoxin on the membrane transport and metabolism of thymidine in Ehrlich ascites tumor cells. Uptake of 3H after exposure of cells to [3H]-thymidine is characterized by a rapid initial velocity that approximates membrane transport followed by a slower rate of uptake that parallels the accumulation of phosphorylated derivatives of thymidine, pri...

Taxol, a natural plant product that enhances the rate and extent of microtubule assembly in vitro and stabilizes microtubules in vitro and in cells, was labeled with tritium by catalytic exchange with (3)H(2)O. The binding of [(3)H]taxol to microtubule protein was studied by a sedimentation assay. Microtubules assembled in the presence of [(3)H]taxol bind drug specifically with an apparent bind...

Intraperitoneal or intraocular (io) injection of tubulin-binding drugs in goldfish, Carassius auratus L., inhibited axonal regeneration or restoration of functional synapses in optic axons following optic nerve crush. One eye was used to detect effects on regeneration and the other was kept intact to detect effects on maintenance of established optic circuits. Regeneration was assessed by measu...

Inhibition of mitosis by many drugs that bind to tubulin has been attributed to depolymerization of microtubules. However, we found previously that low concentrations of vinblastine and vincristine blocked mitosis in HeLa cells with little or no depolymerization of spindle microtubules, and spindles appeared morphologically normal or nearly normal. In the present study, we characterized the eff...

Leishmania microtubules play an important role not only in cell division, but also in keeping the shape of the parasite and motility of its free-living stages. Microtubules result from the self-assembly of alpha and beta tubulins, two phylogenetically conserved and very abundant eukaryotic proteins in kinetoplastids. The colchicine binding domain has inspired the discovery and development of se...

Podophyllin, a crude plant extract with low efficacy, high toxicity, and a serious mutagenicity profile does not comply with the WHO guidelines for plant derived treatments and should be removed from clinical treatment protocols. Home treatment with pharmaceutical products based on podophyllotoxin-the purified, standardised active antiwart ingredient of podophyllin-represents safe and effective...

Biotransformation of podophyllotoxin (PT) by several microbial species has been investigated. Among the fungi tested, it was found that Penicillium strains can isomerize PT to picropodophyllin (PPT) in 8% yield and other strains also transform the substrate into the same product but with lower yield.

These studies explore the effects of an epipodophyllotoxin on the membrane transport and metabolism of thymidine in Ehrlich ascites tumor cells. Uptake of 3H after exposure of cells to [3H]thymidine is characterized by a rapid initial velocity that approx imates membrane transport followed by a slower rate of uptake that parallels the accumulation of phosphorylated derivatives of thymidine, pri...

We have previously found (Ludueña, R. F., and Roach, M. C. (1981b) Biochemistry 20, 4444-4450) that colchicine and podophyllotoxin inhibit the alkylation of tubulin by iodo[14C]acetamide and the formation of an intrachain cross-link in the beta-tubulin subunit by N,N'-ethylenebis(iodoacetamide) (EBI). It was not clear whether these effects were due to conformational changes in tubulin induced b...