Biocatalytic Regioselective O-acylation of Sesquiterpene Lactones from Chicory: A Pathway to Novel Ester Derivatives.

We report the first biocatalytic modification of sesquiterpene lactones (STLs) found in the chicory plants, specifically lactucin (Lc), 11ß,13-dihydrolactucin (DHLc), lactucopicrin (Lp), and 11ß,13-dihydrolactucopicrin (DHLp). The selective O-acylation of their primary alcohol group was carried out by the lipase B from Candida antarctica (CAL-B) using various aliphatic vinyl esters as acyl donors. Perillyl alcohol, a simpler monoterpenoid, served as a model to set up the desired O-acetylation reaction by comparing the use of acetic acid and vinyl acetate as acyl donors. Similar conditions were then applied to DHLc, where five novel ester chains were selectively introduced onto the primary alcohol group, with conversions going from >99 % (acetate and propionate) to 69 % (octanoate). The synthesis of the corresponding O-acetyl esters of Lc, Lp, and DHLp was also successfully achieved with near-quantitative conversion. Molecular docking simulations were then performed to elucidate the preferred enzyme-substrate binding modes in the acylation reactions with STLs, as well as to understand their interactions with crucial amino acid residues at the active site. Our methodology enables the selective O-acylation of the primary alcohol group in four different STLs, offering possibilities for synthesizing novel derivatives with significant potential applications in pharmaceuticals or as biocontrol agents.

Therapeutic properties of dihydroxy-dibutylether on sub-acute liver damage induced by several hepatotoxic agents in rats.

The data presently reported show that repeated exposure of rats to allyl alcohol, ethionine or alpha-naphthyl isothiocyanate (ANIT) impaired some plasmatic parameters mainly by means of different mechanisms which involve the liver function. In particular, four administrations of allyl alcohol, given every other day, increased glutamate oxaloacetate transaminase (GOT) for at least 48 hours from the last dose; ethionine reduced the bromsulphthalein (BSP) clearance even after 48 hours from the 1st, 2nd, or 3rd administration given on the 1st, 5th, or 12th day; ANIT, administered daily for seven days, increased glutamate pyruvate transaminase (GPT), alkaline phosphatase (AP), bilirubin, triglycerides (TG) and cholesterol (CH) while it decreased the body-weight and retarded growth for at least six to seven days after intoxication. Twice daily administrations of dihydroxy-dibutylether (DHBE), a strong choleretic agent, brought to normality the parameters impaired by the three hepatointoxicating agents even when the intoxication was already established. In fact, DHBE reduced the plasma GOT levels increased by allyl alcohol, improved the BSP clearance impaired by ethionine and tended to normalize the parameters modified by ANIT by lowering GPT, AP, CH, TG and bilirubin plasma levels and by enhancing body growth. The curative activity of DHBE does not seem to be related only to a membrane stabilizing action since silymarin, a known cell membrane stabilizer, does not significantly influence the parameters described above in all the experimental conditions. Even the choleretic activity of DHBE alone might not be sufficient to explain its hepatoprotective action since fenipentol (a known choleretic agent) is inactive at least after ANIT intoxication.

DNA fragmentation in N-diazoacetylglycine amide-treated cells determined, by the rate of strand separation in alkali with hydroxylapatite chromatography in batch.

DNA damage induced in mammalian cells (CHO-K1) by one hour treatment with several concentrations of N-diazoacetylglycine amide (DGA) was evaluated by the method of DNA denaturation in alkali and successive neutralization followed by separation of single from double stranded DNA with the recently described technique of hydroxylapatite chromatography performed in batch. This latter technique does not need complex apparatus and simplifies the simultaneous handling of large number of samples; it also appears as sensitive and reliable as the DNA alkaline elution on filter, to which it can be regarded as both alternative and complementary.