norbadione-a and pulvinic-acid

A high-throughput screening method has highlighted the marked antioxidant activity of some pulvinic acid derivatives (PADs) towards oxidation of thymidine, under γ and UV irradiation, and Fenton-like conditions. Here, we report the synthesis of a series of new hydrophilic PADs and the evaluation of their radioprotective efficacy in cell culture. Using a cell-based fluorescent assay, we show that some of these compounds have a pronounced ability to prevent cell death caused by radiation and to allow the subsequent resumption of proliferation. Thus, PADs may be considered as a novel class of radioprotective agents.

Topics: 4-Butyrolactone; Carboxylic Acids; Cell Line; High-Throughput Screening Assays; Humans; Lactones; Phenylacetates; Radiation-Protective Agents; Ultraviolet Rays

We report a quantum mechanical (QM) and classical molecular dynamics (MD) study of the conformational and complexation properties of norbadione-A (NBA), a key pigment involved in the Cs+ complexation by mushrooms. The Z versus E isomers of its pulvinic moieties are compared in their neutral (Pulv0), mono- (Pulv(-1)) and di-deprotonated (Pulv(-2)) states, and the 1H chemical shifts are calculated ab initio. Pulv(-1) is found to be stabilized in the E form by an internal COOH(-)O(enolate) hydrogen-bond. No energy minimum is found for the corresponding COO(-)HO(enol) state, indicating that the conjugated enol function of Pulv0 is more acidic than the COOH function. Further deprotonation leads to the Z and E forms of Pulv(-2) that are close in energy and both account for a marked downfield shift delta of ortho-H8 protons. A similar shift is found upon deprotonation of the enol function of an ester analogue of Pulv0. Therefore, contrary to previous assumptions (ref. 7: P. Kuad, et al., J. Am. Chem. Soc., 2005, 127, 1323), the large shift of delta(H8) around pH 9.5 upon deprotonation of NBA or of pulvinic acid cannot be taken as an indicator of an E-to-Z conformational switch, but merely reflects the pH-induced conformational change of the carboxylate group adjacent to the (H8)-ring. The QM and MD studies on NBA(2-) and NBA(4-) support the view that both species prefer the E/E form with two intramolecular COOH(-)O(enolate) hydrogen-bonds in the gas phase and in solution. Finally, we simulated mono- and di-nuclear complexes of Cs+ with NBA(2-) and NBA(4-) by MD, showing that only the NBA(4-) state populated at high pH values can bind two Cs+ cations, with both E and Z conformations of the pulvinic arms.

Topics: 4-Butyrolactone; Agaricales; Carboxylic Acids; Cations; Cesium; Esters; Gases; Lactones; Methanol; Methylation; Models, Molecular; Molecular Conformation; Phenylacetates; Protons; Quantum Theory; Stereoisomerism; Thermodynamics

A recently reported high-throughput screening strategy has been applied to the rapid selection of new water-soluble antioxidants that display strong protective activities. Based on a competitive immunoassay, a triple-screening procedure was used to evaluate the ability of different compounds to protect thymidine under different oxidative stresses. The pro-oxidant effect of norbadione A in the presence of iron was observed, while some pulvinic acid derivatives proved strongly protective during gamma radiolysis, UV irradiation, and Fenton-like oxidation.

Topics: 4-Butyrolactone; Antioxidants; Carboxylic Acids; Chromatography, High Pressure Liquid; Evaluation Studies as Topic; Flavonoids; Immunoassay; Lactones; Oxidants; Oxidative Stress; Phenols; Phenylacetates; Polyphenols; Quercetin; Reactive Oxygen Species; Thymidine

Topics: 4-Butyrolactone; Basidiomycota; Carboxylic Acids; Dimerization; Lactones; Molecular Structure; Phenylacetates; Pigments, Biological