A series of N,4-diaryl-1,3-thiazole-2-amines containing three aromatic rings with an amino linker were designed and synthesized as tubulin inhibitors and evaluated for their antiproliferative activity in three human cancer cell lines. Most of the target compounds displayed moderate antiproliferative activity, and N-(2,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1,3-thiazol-2-amine (10s) was determin...

The signal for retention in the endoplasmic reticulum of the E3/19K protein of adenovirus type 2 is located within the carboxyl-terminal cytoplasmic extension. A synthetic peptide corresponding to this sequence showed affinity for beta-tubulin, could promote tubulin polymerization in vitro, and bound to taxol-polymerized microtubules. When compared with the microtubule binding sequences from tw...

Interference with microtubule polymerization results in cell cycle arrest leading to cell death. Colchicine is a well-known microtubule polymerization inhibitor which does so by binding to a specific site on tubulin. A set of 3', 4'-bis (substituted phenyl)-4'H-spiro [indene-2, 5'-isoxazol]-1(3H)-one derivatives with known antiproliferative activities were evaluated for their tubulin binding mo...

The Vinca alkaloids differ in their chemotherapeutic effectiveness and their toxicities. To determine whether differences are due to a differential effect on the assembly of tubulin into microtubules, we examined the effects of vincristine, vinblastine, and a newer alkaloid, desacetyl vinblastine amide, on the assembly of bovine brain tubulin in vitro. The three compounds block bovine tubulin p...

A heat stable protein essentail for microtubule assembly has been isolated. This protein, which we designate tau (tau), is present in association with tubulin purified from porcine brain by repeated cycles of polymerization. Tau is separated from tubulin by ion exchange chromatography on phosphocellulose. In the absence of tau, tubulin exists entirely as a 6S dimer of two polypeptide chains (al...

The anticancer drug paclitaxel (Taxol) has been converted to a large number of 2-debenzoyl-2-aroyl derivatives by three different methods. The bioactivities of the resulting analogues were determined in both tubulin polymerization and cytotoxicity assays, and several analogues with enhanced activity as compared with paclitaxel were discovered. Correlation of cytotoxicity in three cell lines wit...

A series of Vinca alkaloids were found to block polymerization of crude tubulin extracts of porcine brain in a dose-dependent manner. This appears to be a specific effect occurring at low concentrations of drug. The concentration of vinblastine that prevents polymerization by 50% was 4.3 x 10(-7) mole/liter for a tubulin concentration of 3.0 mg/ml, and this concentration is consistent with leve...

A series of tubulysin analogs in which one of the stereogenic centers of tubuphenylalanine was eliminated were synthesized. All compounds were tested for antiproliferative activity towards ovarian cancer cells and for inhibition of tubulin polymerization. The dimethyl analogs were generally more active than the desmethyl analogs, and four analogs have tubulin polymerization IC(50) values simila...

The combretastatins (cis-stilbenoid molecules) have received significant interest because of their simple chemical structures, excellent antiproliferative activity, and novel anti-tubulin molecular mechanism action. Significant efforts been carried out aiming at stabilizing the active cis-isomers. A new series cis-vinylamide derivatives containing trimethoxyphenyl moiety were synthesized charac...

Tau protein from mammalian brain promotes microtubule polymerization in vitro and is induced during nerve cell differentiation. However, the effects of tau or any other microtubule-associated protein on tubulin assembly within cells are presently unknown. We have tested tau protein activity in vivo by microinjection into a cell type that has no endogenous tau protein. Immunofluorescence shows t...