Graziella Tocco

Immobilization of catalysts derived from Cinchona alkaloids on modified poly(ethylene glycol)

Abstract The straightforward immobilization of some derivatives of Cinchona alkaloids on modified poly(ethylene glycol)s is reported. The compounds, obtained by simple reactions exploiting different sites for the attachment of the alkaloids to the polymer, were tested as catalysts in the enantioselective benzylation of the benzophenone imine of glycine t -butyl ester (ee up to 64%) and in the conjugate addition of thiophenol to cyclohexenone (ee 22%). The observed stereoselectivities were compared to those obtained either with the unsupported catalysts or with the catalysts immobilized on different polymeric matrixes. The influence of the poly(ethylene glycol) moieties on the catalytic activity is discussed.

Synthesis of a poly(ethylene glycol)-supported tetrakis ammonium salt: a recyclable phase-transfer catalyst of improved catalytic efficiency

The immobilization of four quaternary ammonium groups on a poly(ethylene glycol) support provided an efficient and recyclable phase-transfer catalyst.

Active site and allosteric inhibitors of the ribonuclease H activity of HIV reverse transcriptase

Despite the wealth of information available for the reverse transcriptase (RT)-associated ribonuclease H (RNaseH) domain of lentiviruses, gammaretroviruses and long terminal repeat containing retrotransposons, exploiting this information in the form of an RNaseH inhibitor with high specificity and low cellular toxicity has been disappointing. However, it is now becoming increasingly evident that the two-subunit HIV-1 RT is a highly versatile enzyme, undergoing major structural alterations in order to interact with, position and ultimately hydrolyze the RNA component of an RNA/DNA hybrid. Thus, in addition to targeting the RNaseH active site, identifying small molecules that bind elsewhere and disrupt catalysis allosterically by impairing conformational flexibility is gaining increased attention. This review summarizes current progress towards development of both active site and allosteric RNaseH inhibitors.

Nematicidal Activity of Mint Aqueous Extracts against the Root-Knot Nematode Meloidogyne incognita

The nematicidal activity and chemical characterization of aqueous extracts and essential oils of three mint species, namely, Mentha × piperita , Mentha spicata , and Mentha pulegium , were investigated. The phytochemical analysis of the essential oils was performed by means of GC-MS, whereas the aqueous extracts were analyzed by LC-MS. The most abundant terpenes were isomenthone, menthone, menthol, pulegone, and carvone, and the water extracts yielded mainly chlorogenic acid, salvianolic acid B, luteolin-7-O-rutinoside, and rosmarinic acid. The water extracts exhibited significant nematicidal activity against Meloidogyne incognita , and the EC50/72h values were calculated at 1005, 745, and 300 mg/L for M. × piperita, M. pulegium, and M. spicata, respectively. Only the essential oil from M. spicata showed a nematicidal activity with an EC50/72h of 358 mg/L. Interestingly, menthofuran and carvone showed EC50/48h values of 127 and 730 mg/L, respectively. On the other hand, salicylic acid, isolated in the aqueous extracts, exhibited EC50 values at 24 and 48 h of 298 ± 92 and 288 ± 79 mg/L, respectively.

Potent nematicidal activity of phthalaldehyde, salicylaldehyde, and cinnamic aldehyde against Meloidogyne incognita.

The nematicidal activity of selected aromatic aldehydes was tested against the root knot nematode Meloidogyne incognita. The most active aldehyde was phthalaldehyde (1) with an EC(50) value of 11 ± 6 mg/L followed by salicylaldehyde (2) and cinnamic aldehyde (3) with EC(50) values of 11 ± 1 and 12 ± 5 mg/L, respectively. On the other hand, structurally related aldehydes such as 2-methoxybenzaldehyde (21), 3,4-dimethoxybenzaldehyde, and vanillin (23) were not active at the concentration of 1000 mg/L. By liquid chromatography-mass spectrometry the reactivity of tested aldehydes against a synthetic peptide resembling the nematode cuticle was characterized. At the test concentration of 1 mM, the main adduct formation was observed for 3,4-dihydroxybenzaldehyde (22), 2-methoxybenzaldehyde (21), and 3,4-dimethoxybenzaldehyde. Considering that 2-methoxybenzaldehyde (21) and 3,4-dimethoxybenzaldehyde were not active against M. incognita in in vitro experiments led us to hypothesize a different mechanism of action rather than an effect on the external cuticle modification of nematodes. When the toxicity of the V-ATPase inhibitor pyocyanin (10) was tested against M. incognita J2 nematodes, an EC(50) at 24 h of 72 ± 25 mg/L was found. The redox-active compounds such as phthalaldehyde (1) and salicylaldehyde (2) may share a common mode of action inhibiting nematode V-ATPase enzyme. The results of this investigation reveal that aromatic redox-active aldehydes can be considered as potent nematicides, and further investigation is needed to completely clarify their mode of action.

PEG-immobilization of cardol and soluble polymer-supported synthesis of some cardol–coumarin derivatives: Preliminary evaluation of their inhibitory activity on mushroom tyrosinase

In this work, the PEG-immobilization and the liquid phase synthesis of some coumarins derived from cardol are presented. Some preliminary results on their tyrosinase inhibitory activity are also included.

Nematicidal activity of 2-thiophenecarboxaldehyde and methylisothiocyanate from caper (Capparis spinosa) against Meloidogyne incognita.

New pesticides based on plant extracts have recently gained interest in the development of nontoxic crop protection chemicals. Numerous research studies are focused on the isolation and identification of new active compounds derived from plants. In this manuscript we report about the use of the Mediterranean species Capparis spinosa as a potent natural nematicidal agent against the root knot nematodes Meloidogyne incognita. Leaves, stems, and caper buds of Capparis spinosa were used to obtain their methanol extracts (LME, SME, BME) that were successively in vitro tested against second stage nematode juveniles (J2). In terms of paralysis induction, the methanol extract of the stem part (SME) was found more effective against M. incognita and then the caper methanol buds and leaves extracts. The chemical composition analysis of the extracts carried out by GC/MS and LC/MS techniques showed that methylisothiocyanate was the main compound of SME. The EC50 for SME after 3 days of immersion was 215 ± 36 mg/L. The constituent components of SME such as 2-thiophenecarboxaldehyde and methylisothiocyanate were successively in vitro tested for their nematicidal activity against J2. Both compounds induced paralysis on root knot nematodes ranking first (EC50 = 7.9 ± 1.6, and 14.1 ± 1.9 mg/L respectively) for M. incognita. Moreover, 2-thiophenecarboxaldehyde showed a strong fumigant activity.

Tulipaline A: structure-activity aspects as a nematicide and V-ATPase inhibitor.

Carbonyl groups are known to form covalent adducts with endogenous proteins, but so far, their nematicidal mechanism of action of has been overlooked. The nematicidal activity of ten lactones was tested in vitro against the root knot nematodes Meloidogyne incognita and Meloidogynearenaria. In particular, the saturated lactones α-methylene-γ-butyrolactone or tulipaline A (1) and γ-butyrolactone (3) were active against M. incognita with an EC50/48h of 19.3±10.0 and 40.0±16.2mg/L respectively. Moreover the α, β-unsaturated lactone 5,6-dihydro-2H-pyran-2-one (2) exhibited the strongest nematicidal activity against the two species with EC50/48h 14.5±5.3 and 21.2±9.7mg/L respectively. Here we propose that the toxic effects of lactones and aldehydes on M.incognita and M. arenaria might be a consequence of their vacuolar-type H(+)-ATPase (V-ATPase) inhibition activity; in fact α-methylene-γ-butyrolactone (1) and salicylaldehyde (12) produced an increased pH in lysosomal-like organelles on HeLa human cell line and this alteration was most likely related to a V-ATPase impairment.

Nematicidal Activity of the Volatilome of Eruca sativa on Meloidogyne incognita.

Research on new pesticides based on plant extracts, aimed at the development of nontoxic formulates, has recently gained increased interest. This study investigated the use of the volatilome of rucola (Eruca sativa) as a powerful natural nematicidal agent against the root-knot nematode, Meloidogyne incognita. Analysis of the composition of the volatilome, using GC-MS-SPME, showed that the compound (Z)-3-hexenyl acetate was the most abundant, followed by (Z)-3-hexen-1-ol and erucin, with relative percentages of 22.7 ± 1.6, 15.9 ± 2.3, and 8.6 ± 1.3, respectively. Testing of the nematicidal activity of rucola volatile compounds revealed that erucin, pentyl isothiocyanate, hexyl isothiocyanate, (E)-2-hexenal, 2-ethylfuran, and methyl thiocyanate were the most active with EC50 values of 3.2 ± 1.7, 11.1 ± 5.0, 11.3 ± 2.6, 15.0 ± 3.3, 16.0 ± 5.0, and 18.1 ± 0.6 mg/L, respectively, after 24 h of incubation. Moreover, the nematicidal activity of fresh rucola used as soil amendant in a containerized culture of tomato decreased the nematode infection in a dose-response manner (EC50 = 20.03 mg/g) and plant growth was improved. On the basis of these results, E. sativa can be considered as a promising companion plant in intercropping strategies for tomato growers to control root-knot nematodes.

Mild Synthetic Approach to Novel Indole-1-Carbinols and Preliminary Evaluation of Their Cytotoxicity in Hepatocarcinoma Cells

A mild and versatile method for the synthesis of some novel indole‐1‐carbinols has been developed via one‐pot reaction of indoles and paraformaldehyde in the presence of an excess of CaO, MgO, ZnO or TiO2. The solvent‐free reaction provided all the indole derivatives in moderate to good yields and short reaction times. Moreover, the effect of some selected indole‐1‐carbinols on cell proliferation of the hepatoma cell line FaO was evaluated.