Chemical Analysis and In Vitro Bioactivity of Essential Oil of Laurelia sempervirens and Safrole Derivatives against Oomycete Fish Pathogens.

In this study, the essential oil (EO) from Laurelia sempervirens was analyzed by GC/MS and safrole (1) was identified as the major metabolite 1, was subjected to direct reactions on the oxygenated groups in the aromatic ring and in the side chain, and eight compounds (4 to 12) were obtained by the process. EO and compounds 4-12 were subjected to biological assays on 24 strains of the genus Saprolegnia, specifically of the species 12 S. parasitica and 12 S. australis. EO showed a significant effect against Saprolegnia strains. Compound 6 presents the highest activity against two resistant strains, with minimum inhibitory concentration (MIC) and minimum oomyceticidal concentration (MOC) values of 25 to 100 and 75 to 125 µg/mL, respectively. The results show that compound 6 exhibited superior activities compared to the commercial controls bronopol and azoxystrobin used to combat these pathogens.

Exploring the Use of a Guanine-Rich Catalytic DNA for Sulfoxide Preparation.

A guanine-rich DNA oligonucleotide complexed with hemin was used to catalyze controlled oxygen transfer reactions to different sulfides for sulfoxide preparation in the presence of H2O2. Comparable activities were obtained when using fully modified L-DNA. In addition, oligonucleotide immobilization led to an active catalyst which could be successfully recovered and reused without loss of activity.

Novel furfurylidene N-acylhydrazones derived from natural safrole: discovery of LASSBio-1215, a new potent antiplatelet prototype.

We describe herein the discovery of (E)-N-methyl-N'-((5-nitrofuran-2-yl)methylene)benzo[d]( 1 , 3 ) dioxole-5-carbohydrazide (9e), named LASSBio-1215, as a novel antiplatelet agent belonging to the N-methyl-N-acylhydrazone class, which exert their antiaggregating actions on human and rabbit platelets induced by different agonists, through cyclooxygenase-1 (COX-1) or thromboxane synthase inhibition. This compound was elected after screening of a series of functionalized furyl N-acylhydrazone derivatives, synthesized from natural safrole 10. In vitro assays showed that compound 9e presents platelet-aggregating activity in rabbit platelet-rich plasma (PRP) induced by arachidonic acid (IC(50) = 0.7 µM) and collagen (IC(50) = 4.5 µM). Moreover, LASSBio-1215 also inhibited almost completely the second wave of adenosine diphosphate-induced platelet aggregation in human PRP, and this effect was correlated with their ability to block the production of pro-aggregating autacoid thromboxane A(2).

Synthesis and analgesic profile of conformationally constrained N-acylhydrazone analogues: discovery of novel N-arylideneamino quinazolin-4(3H)-one compounds derived from natural safrole.

In this work we reported the synthesis and evaluation of the analgesic, anti-inflammatory, and platelet anti-aggregating properties of new 3-(arylideneamino)-2-methyl-6,7-methylenedioxy-quinazolin-4(3H)-one derivatives (3a-j), designed as conformationally constrained analogues of analgesic 1,3-benzodioxolyl-N-acylhydrazones (1) previously developed at LASSBio. Target compounds were synthesized in very good yields exploiting abundant Brazilian natural product safrole (2) as starting material. The pharmacological assays lead us to identify compounds LASSBio-1240 (3b) and LASSBio-1272 (3d) as new analgesic prototypes, presenting an antinociceptive profile more potent and effective than dipyrone and indomethacin used, respectively, as standards in AcOH-induced abdominal constrictions assay and in the formalin test. These results confirmed the success in the exploitation of conformation restriction strategy for identification of novel cyclic N-acylhydrazone analogues with optimized analgesic profile.

Design and synthesis of 3,4-methylenedioxy-6-nitrophenoxyacetylhydrazone derivatives obtained from natural safrole: new lead-agents with analgesic and antipyretic properties.

In this work, we reported the synthesis and evaluation of the analgesic, anti-inflammatory, and antipyretic properties of new 2-(6-nitro-benzo[1,3]dioxol-5-yloxy)-acetylhydrazone derivatives (3), designed exploring molecular hybridization and isosteric replacement approaches between nimesulide (1) and carbanalogue NAH series (2) developed at LASSBio. Target compounds were synthesized in very good yields exploiting abundant Brazilian natural product safrole (4) as starting material. The evaluation of the antinociceptive properties of this series led us to discover a new potent prototype of analgesic and antipyretic agent, that is, NAH derivative 3c, named LASSBio-891, which showed to be more potent than dipyrone used as standard.

Synthesis and spectroscopic behavior of highly luminescent Eu(3+)-dibenzoylmethanate (DBM) complexes with sulfoxide ligands.

In this paper the synthesis, characterization and photoluminescent behavior of the [RE(DBM)3L2] complexes (RE=Gd and Eu) with a variety of sulfoxide ligands; L=benzyl sulfoxide (DBSO), methyl sulfoxide (DMSO), phenyl sulfoxide (DPSO) and p-tolyl sulfoxide (PTSO) have been investigated in solid state. The emission spectra of the Eu(3+)-beta-diketonate complexes show characteristics narrow bands arising from the 5D0-->7F(J) (J=0-4) transitions, which are split according to the selection rule for C(n), C(nv) or C(s) site symmetries. The experimental Judd-Ofelt intensity parameters (Omega2 and Omega4), radiative (A(rad)) and non-radiative (A(nrad)) decay rates, and R02 for the europium complexes have been determined and compared. The highest value of Omega2 (61.9x10(-20)cm2) was obtained to the complex with PTSO ligand, indicating that Eu3+ ion is in the highly polarizable chemical environment. The higher values of the experimental quantum yield (q) and emission quantum efficiency of the emitter 5D0 level (eta) for the Eu-complexes with DMSO, DBSO and PTSO sulfoxides suggest that these complexes are promising Light Conversion Molecular Devices (LCMDs). The lower value of quantum yield (q=1%), for the hydrated complex [Eu(DBM)3H2O], indicates that the luminescence quenching occurs via multiphonon relaxation by coupling with the OH-oscillators from water molecule coordinated to rare earth ion. The pure red emission of the Eu-complexes has been confirmed by (x, y) color coordinates.

'Non-covalent synthesis' of a chiral host of calix[6]arene and enantiomeric discrimination.

'Non-covalent synthesis' of novel chiral hosts (calix[6]arene-chiral amine complexes) and its application to enantiomeric discrimination was investigated by (1)H NMR spectroscopy. The topology of a ternary complex was proposed for the calix[6]arene-amine-sulfoxide to rationalize the chiral recognition.

Synthesis, antitumour and antimicrobial activities of new peptidyl derivatives containing the 1,3-benzodioxole system.

Two series of 5 and 6-substituted 1,3-benzodioxole peptidyl derivatives were synthesized and evaluated as antitumour and antimicrobial agents. The compounds that could be conveniently prepared in a few steps processes from natural safrole have been characterised by IR and 1H-NMR spectroscopy. In vivo antitumor activity tests showed that some of the compounds were able to inhibit carcinoma S-180 tumour growth in mice. The in vitro antimicrobial activity of all compounds revealed that they are able to promote the growth of some organisms, including Bacillus subtilis.

Synthesis and analgesic activity of novel N-acylarylhydrazones and isosters, derived from natural safrole.

Anew series of antinociceptive compounds belonging to the N-acylarylhydrazone (NAH) class were synthesized from natural safrole (7). The most analgesic derivative represented by 10f, [(4'-N,N-dimethylaminobenzylidene-3-(3', 4'-methylenedioxyphenyl)propionylhydrazine], was more potent than dipyrone and indomethacin, used as standards. The NAH compounds described herein were structurally planned by molecular hybridization and classical bioisosterism strategies on previously reported analgesic NAH in order to identify the pharmacophoric contribution of the N-acylarylhydrazone moiety and investigate the structure-activity relationship (SAR) in these series.

Synthesis and pharmacological evaluation of new flosulide analogues, synthesized from natural safrole.

Four new aryl-sulfonamide derivatives (3a, 4a, 5a-b), having methylenedioxy group attached to phenyl ring, were prepared from natural safrole and evaluated as anti-inflammatory agents. The N-methylsulfonamide 3a and corresponding retrosulfonamide derivative 5a were more active than standards indomethacin and nimesulide, at the same molar concentration, in carrageenan-induced pleurisy assay.

The synthesis and anti-inflammatory properties of a new sulindac analogue synthesized from natural safrole.

The synthesis of the new sulindac (3) analogue (Z)-5,6-methylenedioxy-2-methyl-1-(p-methylsulfinylbenzylidene)-3- indenyl acetic acid (1) from natural safrole (2), an abundant natural product occurring as the principal chemical constituent of Sassafraz oil, is described. The principal feature of this route is shortness, stereoselectivity, and high overall yield. The new analogue is produced in a yield of approximately 30% from the natural product. The results include the anti-inflammatory activity of 1 as well as that for its corresponding sulfide (12), a synthetic precursor of 1 that may be an important metabolic product of 1 by analogy to 3 itself. The anti-inflammatory profiles of these derivatives, measured in the carrageenan-induced rat paw edema test, indicated a 50% effective dose of 42 mg/kg for 1 and of 23 mg/kg for 12, confirming the structure-activity relationships of these agents. These results indicate that the new analogue 1 could represent a prodrug with a similar therapeutic profile to that of the pharmaceutical product 3.

Estudo de espectros de ressonância magnética nuclear protônica e de carbono 13 de uma série de derivados de alilfenóis / Study of proton and carbon 13 nuclear magnetic ressonance spectra of an allylphenol derivatives series

Sais de amônio quaternários derivados de alilfenóis naturais foram sintetizados com o objetivo de se obter analgésicos periféricos, Eugenol, Ometileugenol e safrol foram submetidos a nitraçäo, reduçäo e permetilaçäo. As aminas também foram transformadas nos respectivos cloridratos. Os espectros de RMN1 H dos nitrocompostos, aminas, cloridratos de aminas, sais de amônio quaternários e dimetilaminas foram analisados, assim como os espectros de RMN13 C dos nitrocompostos e dos sais de amônio quaternários.