Phenolic acid derivatives with potential anticancer properties--a structure-activity relationship study. Part 1: methyl, propyl and octyl esters of caffeic and gallic acids.

The antiproliferative and cytotoxic properties of polyphenolic acid derivatives, structurally related with the natural models caffeic and gallic acids, have been tested in human cervix adenocarcinoma cells (HeLa). Simultaneous structural information was obtained for these compounds through theoretical ab initio methods. This study was conducted for the following esters: methyl caffeate (MC, 1), propyl caffeate (PC, 2), octyl caffeate (OC, 3), methyl gallate (MG, 4), propyl gallate (PG, 5) and octyl gallate (OG, 6). A significant growth-inhibition effect was assessed for some of these compounds, clearly dependent on their structural characteristics. Marked structure-activity relationships (SARs)--namely the number of hydroxyl ring substituents--were found to rule the biological effect of such systems.

Excited levels in 149Pm from the decay of 149Nd.

The level structure of 149Pm has been investigated by studying the gamma rays emitted following the beta(-) decay of 149Nd (T(1/2)=1.7h). The singles and the gammagamma coincidence spectra were taken using HPGe detectors with high energy resolution. The energy and relative intensities of 198 gamma rays have been determined, 45 for the first time and several multiplets were resolved using bidimensional data analysis. A decay scheme with 51 levels has been proposed. This includes 6 new levels, at 1407, 1368, 1364, 1329, 1293 and 1181keV. The present results permitted assignments of spin and parity for a number of these levels.

Energy levels in 139La from the decay of 139Ba.

The gamma-ray spectrum of 139La following the beta- decay of 139Ba has been studied using both singles and gammagamma coincidence spectroscopy techniques. The energies and intensities of 30 gamma-transitions have been determined, which include three new transitions placed in the level scheme. Two new levels at 1524.6 and 1900.3 keV excitation energies are proposed and a number of gamma-transitions have been confirmed. On the basis of these results a precise decay scheme is proposed.

Kinetic analysis of the initial steps involved in lipoplex--cell interactions: effect of various factors that influence transfection activity.

We investigated the mode of interaction of lipoplexes (DOTAP:DOPE/DNA) with HeLa cells, focusing on the analysis of the initial steps involved in the process of gene delivery. We evaluated the effect of different factors, namely the stoichiometry of cationic lipids and DNA, the presence of serum in the cell culture medium, and the incorporation of the ligand transferrin into the lipoplexes, on the extent of binding, association and fusion (lipid mixing) of the lipoplexes with the cells. Parallel experiments were performed upon cell treatment with inhibitors of endocytosis. Our results indicate that a decrease of the net charge of the complexes (upon addition of DNA) generally leads to a decrease in the extent of binding, cell association and fusion, except for the neutral complexes. Association of transferrin to the lipoplexes resulted in a significant enhancement of the interaction processes referred to above, which correlates well with the promotion of transfection observed under the same conditions. Besides triggering internalization of the complexes, transferrin was also shown to mediate fusion with the endosomal membrane. The extent of fusion of this type of complexes was reduced upon their incubation with cells in the presence of serum, suggesting that serum components limit the transferrin fusogenic properties. Results were analyzed by using a theoretical model which allowed to estimate the kinetic parameters involved in lipoplex--cell interactions. The deduced fusion and endocytosis rate constants are discussed and compared with those obtained for other biological systems. From the kinetic studies we found a twofold enhancement of the fusion rate constant (f) for the ternary lipoplexes. We also concluded that HeLa cells yield a relatively low rate of endocytosis. Overall, our results estimate the relative contribution of fusion of lipoplexes with the plasma membrane, endocytosis and fusion with the endosomal membrane to their interactions with cells, this information being of crucial importance for the development of gene therapy strategies.

Decay of 72Ga.

The gamma-ray spectrum of 72Ge following the beta- decay of 72Ga has been studied using both single and gamma-gamma coincidence spectroscopy techniques. The energies and intensities of 110 gamma-rays have been determined, 26 of them were observed for the first time and 20 have been confirmed. Of the total number of gamma-rays observed, 95 have been placed in a proposed level scheme containing 31 levels. This includes five new levels at 2303, 2694, 3067, 3097 and 3420 keV.