Ab-initio and experimental study of pentose sugar dehydration mechanism in the gas phase.

In this work pentose sugar (D-xylose, D-ribose and D-arabinose) gas phase dehydration reaction was investigated by means of mass spectrometric techniques and theoretical calculations. The ionic species derived from the dehydration reaction of protonated D-ribose and D-arabinose were structurally characterized by their fragmentation patterns and the relative dehydration energies measured by energy resolved CAD mass spectra. The results were compared with those recently obtained for D-xylose in the same mass spectrometric experimental conditions. Dehydration of C1-OH protonated sugars was theoretically investigated at the CCSD(T)/cc-pVTZ//M11/6-311++G(2d,2p) level of theory. Protonated pentoses are not stable and promptly lose a water molecule giving rise to the dehydrated ions at m/z 133. D-xylose, D-ribose and D-arabinose dehydration follows a common reaction pathway with ionic intermediates and transition states characterized by similar structures. Slightly different dehydration energies were experimentally measured and the relative trend was theoretically confirmed. The overall dehydration activation energy follows the order arabinose < ribose < xylose. Gas-phase pentose sugar dehydration leads to the formation of protonated 2-furaldehyde as final product. Based on the experimental and theoretical evidence a new mechanistic hypothesis starting from C1-OH protonation was proposed.

Curcumin analogues as possible anti-proliferative & anti-inflammatory agents.

A series of novel curcumin analogues has been designed, synthesized and tested in vitro/in vivo as potential multi-target agents. Their anti-proliferative and anti-inflammatory activities were studied. Compounds 1b and 2b were stronger inhibitors of soybean lipoxygenase (LOX) than curcumin. Analogue 1b was also the most potent aldose reductase (ALR2) inhibitor. Two compounds, (1a and 1f) exhibited in vivo anti-inflammatory activity comparable to that of indomethacin, whereas derivative 1i exhibited even higher activity. The derivatives were also tested for their anti-proliferative activity using three different human cancer cell lines. Compounds 1a, 1b, 1d and 2b exhibited significant growth inhibitory activity as compared to curcumin, against all three cancer cell lines. Lipophilicity was determined as R(M) values using RPTLC and theoretically. The results are discussed in terms of the structural characteristics of the compounds. Docking simulations were performed on LOX and ALR2 inhibitor 1b and curcumin. Compound 1b is well fitted in the active site of ALR2, binding to the ALR2 enzyme in a similar way to curcumin. Allosteric interactions may govern the LOX-inhibitor binding.