Medicinal chemistry depends on many other disciplines ranging from organic chemistry andpharmacology to computational chemistry. Typically medicinal chemists use the moststraightforward ways to prepare compounds. The validation of any design project comes from thebiological testing.Studies of the binding site of vinblastine by a single cross—linking experiment identified it asbeing between resi...

Previous ultrastructural studies appear to indicate that the lacinate appendages (highly elaborated laminar structures which cover the surface of moth spermatozoa) may be intracellular derivatives of transient microtobules found in the elongating spermatids of these insects. Additional support for this theory is supplied by the present study in which testes of the warehouse moth Ephestia cautel...

Use of a bis-dithiane deprotection-tandem bis-spiroacetalisation sequence was key to the successful synthesis of the [5,6,6]-bis-spiroacetal of the antimitotic agent spirastrellolide B, achieved in a highly convergent fashion involving successive dithiane alkylations.

Recently, we have proposed a nutrient-limited model for the avascular growth of tumors including cell proliferation, motility, and death [S. C. Ferreira, Jr., M. L. Martins, and M. J. Vilela, Phys. Rev. E 65, 021907 (2002)], which qualitatively reproduces commonly observed morphologies for carcinomas in situ. In the present work, we analyze the effects of distinct chemotherapeutic strategies on...

The hydrophobic patch of cyclins interacts with cyclin-dependent kinase (Cdk) substrates and p27-type Cdk inhibitors. Although this interaction is assumed to contribute to the specificity of different Cdk-Cyclin complexes, its role in specific steps of the cell cycle has not been demonstrated. Here, we show that in Drosophila the mitotic inhibitor Frühstart (Frs) binds specifically and with hig...

Intervention of cancer cell mitosis by antitubulin drugs is among the most effective cancer chemotherapies. However, antitubulin drugs have dose-limiting side effects due to important functions of microtubules in resting normal cells and are often rendered ineffective by rapid emergence of resistance. Antimitotic agents with different mechanisms of action and improved safety profiles are needed...

Several diagnostic techniques have been employed for the detection of Trichomonas vaginalis. Microtubules constitute the cytoskeleton in eukaryotic cells and are sensitive to antimitotic drugs, such as Taxol (paclitaxel). We used FLUTAX a fluorescent taxoid - to analyze the microtubule distribution in living trophozoites of T. vaginalis in urine and in vaginal discharge. A high intensity of flu...

The synthesis of 2-α-styrylpyridines has been carried out by using the coupling of polyoxygenated N-tosylhydrazones with various 2-halopyridines. We demonstrated that the use of a catalytic amount of PdCl2(MeCN)2 in combination with a bidentate ferrocene DPPF or a monodentate alkyl phosphine (t)Bu2MeP-HBF4 constitutes an efficient protocol for this coupling, providing 2-α-styrylpyridines 2 in s...

Dolastatin 10 is a highly cytotoxic antimitotic peptide in phase II clinical trials. Its cytotoxicity has been as much as 50-fold greater than that of vinblastine, despite quantitatively similar effects of the two drugs on tubulin polymerization. We compared uptake and efflux of radiolabeled dolastatin 10 and vinblastine in human Burkitt lymphoma CA46 cells to gain an understanding of the great...