thiourea and cupric-chloride

An intramolecular Diels-Alder (IMDA) reaction efficiently accelerated by Schreiner's thiourea is reported, to build a functionalized cytochalasin scaffold (periconiasin series) for biological purposes. DFT calculation highlighted a unique multidentate cooperative hydrogen bonding in this catalysis. The deprotection end game afforded a collection of diverse structures and showed the peculiar reactivity of the Diels-Alder cycloadducts upon functionalization. Biological studies revealed strong cytotoxicity of a few compounds on breast cancer cell lines while actin polymerization is preserved.

Topics: Actin Cytoskeleton; Antineoplastic Agents; Catalysis; Cell Line, Tumor; Cell Survival; Copper; Crystallography, X-Ray; Cycloaddition Reaction; Cytochalasins; Humans; Hydrogen Bonding; Molecular Conformation; Palladium; Stereoisomerism; Thermodynamics; Thiourea

The detection of DNA radicals by immuno-spin trapping (IST) is based on the trapping of radicals with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), forming stable nitrone adducts that are then detected using an anti-DMPO serum. DNA radicals are very reactive species, and because they are paramagnetic they have previously been detected only by electron spin resonance (ESR) with or without spin trapping, which is not available in most bioresearch laboratories. IST combines the simplicity, reliability, specificity and sensitivity of spin trapping with heterogeneous immunoassays for the detection of DNA radicals, and complements existing methods for the measurement of oxidatively generated DNA damage. Here we have used IST to demonstrate that DMPO traps Cu(II)-H(2)O(2)-induced DNA radicals in situ and in real time, forming DMPO-DNA nitrone adducts, but preventing both 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) formation and DNA fragmentation. We also applied IST to detect DNA radicals in rat hepatocytes exposed to Cu(II) and H(2)O(2) under nonlethal conditions.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Ascorbic Acid; Cell Nucleus; Chlorides; Copper; Cyanides; Cyclic N-Oxides; Deoxyguanosine; Deuterium Oxide; DNA; DNA Fragmentation; Enzyme-Linked Immunosorbent Assay; Female; Free Radicals; Glutathione; Hepatocytes; Histidine; Hydrogen Peroxide; Immunoassay; Nitrogen Oxides; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Spin Trapping; Thiourea; Zinc Compounds

PTU markedly enhanced the cytotoxic effects of CuCl2 on chick embryonic PECs cultured in vitro. We investigated this newly discovered effect of PTU and its analogues in relation to the toxic effects of Cu ion. Most PECs maintained in medium containing 0.5 mM PTU were lysed within 4 h by the addition of 0.1 mM CuCl2, which addition killed no PECs in the absence of PTU. The effect of PTU was not specific to PECs. All the cell lines tested, KB, N-18, N-115 and B-16, reacted against exogenous Cu in the presence of PTU as did the PECs. Analogues of PTU had effects on PECs similar to those on PTU in the presence of Cu ion. ANTU had a greater effect than PTU. MTU and TU had less effect than PTU. PTU did not affect the cytolysis induced by the addition of the divalent cations Mn, Co and Zn. About 6-fold the 64Cu-uptake by PECs was scored in the presence of PTU. The relation between this cytotoxic-enhancing effect and other biological activities of PTU are discussed.

Topics: Animals; Carcinoma, Squamous Cell; Cations, Divalent; Cell Division; Cell Line; Cell Survival; Chick Embryo; Copper; Dose-Response Relationship, Drug; Drug Interactions; Epithelium; Humans; Kinetics; Melanoma; Mice; Neuroblastoma; Phenylthiourea; Pigmentation; Thiourea