Antifungal derivatives from Piper mollicomum and P. lhotzkyanum (Piperaceae)

Bioguided fractionation of the extracts from leaves of Piper mollicomum and Piper lhotzkyanum against the fungi Cladosporium cladosporioides and C. sphaerospermum afforded seven bioactive compounds, four being chromenes: methyl 2,2-dimethyl-2H-chromene-6-carboxylate, methyl 8-hydroxy-2,2-dimethyl-2H-chromene-6-carboxylate, 2-methyl-2-[4'-methyl-3'-pentenyl]-2H-1-benzopyran-6-carboxylic acid, 2,2-dimethyl-2H-chromene-6-carboxylic acid, one a dihydrochalcone: 2',6'-dihydroxy-4'-methoxydihydrochalcone, and two flavanones: 7-methoxy-5,4'-dihydroxy-flavanone and 7,4'-dimethoxy-5-hydroxy-flavanone. The structures of the bioactive isolated derivatives were elucidated by interpretation of their NMR data [¹H and 13C (BBD, DEPT 135º)], and mass spectral data as well as by comparison with data described in the literature.

An easy and direct method for the synthesis of 1,2,4-triazole derivatives through carboxylic acids and hydrazinophthalazine

We have developed an easy method for the synthesis of thirteen compounds derived from 1,2,4-triazoles through a carboxylic acid and hydrazinophthalazine reaction, with a 75-85% yield mediated by the use of agents such as 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide hydrochloride and 1-hydroxybenzotriazole. The operational simplicity of this method and the good yield of products make it valuable for the synthesis of new compounds with pharmacological activity.

Synthesis, antimicrobial and cytotoxic activities of 5-benzylidene-2-[(pyridine-4-ylmethylene)hydrazono]-thiazolidin-4-one and 2-[(pyridine-4-ylmethylene) hydrazono]-thiazolidin-4-one derivatives

A new series of 5-benzylidene-2-[(pyridine-4-ylmethylene)hydrazono]-thiazolidin-4-ones 4a-l have been synthesized. These compounds were designed by a molecular hybridization approach. 2-[(Pyridine-4-ylmethylene)hydrazono]-thiazolidin-4-ones 3a-d were also obtained and used as intermediates to give the target compounds. The in vitro antimicrobial and cytotoxic activities were evaluated for both series. The intermediate 3b showed considerable antibiotic activity against B. subtilis and C. albicans. In the cytotoxic activity compounds 3b (IC50= 4.25 ± 0.36 µg/mL) and 4l (IC50= 1.38 ± 0.04 µg/mL) were effective for inhibition of human erythromyeloblastoid leukemia (K-562) and human lung carcinoma (NCI-H292) cell lines, respectively.

Contribuição da densidade do PSA para predizer o câncer da próstata em pacientes com valores de PSA entre 2,6 e 10,0 ng/ml

OBJETIVO: Estudar o perfil dos pacientes submetidos a biópsia prostática, determinando possíveis padrões que, associados aos níveis de PSA entre 2,6 e 10,0 ng/ml, possam levar a uma diminuição de biópsias desnecessárias. MATERIAIS E MÉTODOS: De 2007 a 2009, foi realizado um estudo transversal com 1.282 indivíduos submetidos a biópsia prostática e que apresentavam níveis de PSA entre 2,6 e 10,0 ng/ml. RESULTADOS: A prevalência de câncer foi de 28,6%. Pacientes com câncer eram, em média, mais idosos, com valores de PSA e densidade de PSA mais altos e menor volume da próstata. Na análise da densidade de PSA, os pacientes com câncer tiveram média de 0,31 ng/ml/cc, enquanto nos pacientes com resultado negativo a média foi de 0,10 ng/ml/cc. Utilizando como critério de positividade para câncer o ponto de corte de densidade de PSA de 0,15 ng/ml/cc, obtivemos especificidade de 74% e sensibilidade de 70%. Para aumentar a sensibilidade é preciso reduzir o ponto de corte. Com o valor 0,09 ng/ml/cc, obtivemos sensibilidade de 84% (IC 95%: 80-87%) e especificidade de 75% (IC 95%: 72-78%). CONCLUSÃO: O uso sistemático da densidade de PSA na indicação de prosseguimento da investigação do paciente com biópsia poderia reduzir a quantidade de procedimentos desnecessários.

Structural and reactivity analyses of 2-benzylamino-1,4-naphthoquinone by X-ray characterization, electrochemical measurements, and dft single-molecule calculations

This study represents an integrated approach towards understanding the electronic and structural aspects of 2-benzylamino-1,4-naphthalenedione, a representative 2-amino-napfthoquinone. To this end, theoretical calculations performed at the B3PW91/6-31+G(d) level of density functional theory, electrochemical and X-ray structural investigation were employed. Two intramolecular H-bonds and other two intermolecular H-bonds were observed, including non-classical interactions. Cyclic voltammogram (CV) and differential pulse voltammetry (DPV) show two pairs of peaks, being each one a monoelectronic process.

Magnetic, thermal and spectral properties of Ni(II) 2,3- , 3,5- and 2,6-dimethoxybenzoates

Complexes of Ni(II) 2,3-, 3,5- and 2,6-dimethoxybenzoates have been synthesized, their physico-chemical properties have been compared and the influence of the position of -OCH3 substituent on their properties investigated. The analysed compounds are crystalline, hydrated salts with green colour. The carboxylate ions show a bidentate chelating or bridging coordination modes. The thermal stabilities of Ni(II) dimethoxybenzoates were investigated in air in the range of 293-1173 K. The complexes decompose in three steps, yelding the NiO as the final product of decomposition. Their solubilities in water at 293 K are in the order of 10-2-10-4 mol×dm-3. The magnetic susceptibilities for the analysed dimethoxybenzoates of Ni(II) were measured over the range of 76-303 K and the magnetic moments were calculated. The results reveal that the complexes are the high-spin ones and the ligands form the weak electrostatic field in the octahedral coordination sphere of the central Ni(II) ion. The various position -OCH3 groups in benzene ring cause the different steric, mesomeric and inductive effects on the electron density in benzene ring.

Anti-parasitic action and elimination of intracellular Toxoplasma gondii in the presence of novel thiosemicarbazone and its 4-thiazolidinone derivatives

Toxoplasma, which infects all eukaryotic cells, is considered to be a good system for the study of drug action and of the behavior of infected host cells. In the present study, we asked if thiosemicarbazone derivatives can be effective against tachyzoites and which morphological and ultrastructural features of host cells and parasites are associated with the destruction of Toxoplasma. The compounds were tested in infected Vero cell culture using concentration screens (0.1 to 20 mM). The final concentration of 1 mM was chosen for biological assay. The following results were obtained: 1) These new derivatives decreased T. gondii infection with an in vitro parasite IC50% of 0.2-0.7 mM, without a significant effect on host cells and the more efficient compounds were 2, 3 (thiosemicarbazone derivatives) and 4 (thiazolidinone derivative); 2) The main feature observed during parasite elimination was continuous morphological disorganization of the tachyzoite secretory system, progressive organelle vesiculation, and then complete disruption; 3) Ultrastructural assays also revealed that progressive vesiculation in the cytoplasm of treated parasites did not occur in the host cell; 4) Vesiculation inside the parasite resulted in death, but this feature occurred asynchronously in different intracellular tachyzoites; 5) The death and elimination of T. gondii was associated with features such as apoptosis-like stage, acidification and digestion of parasites into parasitophorous vacuoles. Our results suggest that these new chemical compounds are promising for the elimination of intracellular parasites by mainly affecting tachyzoite development at 1 mM concentration for 24 h of treatment.

2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone™ therapy

Apatone™, a combination of menadione (2-methyl-1,4-naphthoquinone, VK3) and ascorbic acid (vitamin C, VC) is a new strategy for cancer treatment. Part of its effect on tumor cells is related to the cellular pro-oxidative imbalance provoked by the generation of hydrogen peroxide (H2O2) through naphthoquinone redox cycling. In this study, we attempted to find new naphthoquinone derivatives that would increase the efficiency of H2O2 production, thereby potentially increasing its efficacy for cancer treatment. The presence of an electron-withdrawing group in the naphthoquinone moiety had a direct effect on the efficiency of H2O2 production. The compound 2-bromo-1,4-naphthoquinone (BrQ), in which the bromine atom substituted the methyl group in VK3, was approximately 10- and 19-fold more efficient than VK3 in terms of oxygen consumption and H2O2 production, respectively. The ratio [H2O2]produced / [naphthoquinone]consumed was 68 ± 11 and 5.8 ± 0.2 (µM/µM) for BrQ and VK3, respectively, indicating a higher efficacy of BrQ as a catalyst for the autoxidation of ascorbic acid. Both VK3 and BrQ reacted with glutathione (GSH), but BrQ was the more effective substrate. Part of GSH was incorporated into the naphthoquinone, producing a nucleophilic substitution product (Q-SG). The depletion of BrQ by GSH did not prevent its redox capacity since Q-SG was also able to catalyze the production of reactive oxygen species. VK3/VC has already been submitted to clinical trials for the treatment of prostate cancer and has demonstrated promising results. However, replacement of VK3 with BrQ will open new lines of investigation regarding this approach to cancer treatment.

More about the role of 2,6-dichlorophenol in tick courtship: identification and olfactometer bioassay in Amblyomma cajennense and Rhipicephalus sanguineus

This study aimed to identify 2,6-dichlorophenol (2,6-DCP) in Amblyomma cajennense and to evaluate its role in A. cajennense and Rhipicephalus sanguineus courtship. Hexanic extract from attractive females was purified by solid phase extraction and the phenol was identified by the single ion monitoring method using GC/MS. In an olfactometer, the responses of A. cajennense and R. sanguineus males to females, control rubber septa or rubber septa impregnated with 2,6-DCP at 50, 500, and 5000 ng, respectively, were studied. 2,6-DCP was identified in A. cajennense extract and the males oriented themselves toward the concentration of 500 ng. These septa and the females were recognized as copula partners. The septa treated with 2,6-DCP did not attract and were not even recognized by the R. sanguineus males, whereas the females were recognized. Due to the presence of 2,6-DCP in A. cajennense and the results of biological bioassays, it was concluded that this compound acts as an attractant and mounting sex pheromone in this tick, but it does not play any role in R. sanguineus courtship.

2,6-di-hidroxiacetofenona no enraizamento de estacas semilenhosas de pessegueiro

A propagação do pessegueiro no Brasil baseia-se na enxertia de cultivares-copa em porta-enxertos propagados por sementes, e uma alternativa de propagação para esta frutífera poderia ser a estaquia. O objetivo deste trabalho foi avaliar o potencial de enraizamento de estacas semilenhosas de cultivares de pessegueiro através da aplicação de 2,6-di-hidroxiacetofonona (2,6-DHAP) antes do tratamento com AIB (ácido indolbutírico). As estacas foram preparadas a partir de ramos coletados das cultivares Delicioso Precoce, Jóia 1 e Okinawa, em dezembro de 2001, para serem tratadas na base com 2,6-DHAP (0 e 300mg L-1), por 4h, em aeração e depois com AIB (200mg L-1 e 2500mg L-1). As estacas foram plantadas em bandejas de poliestireno expandido com vermiculita fina e colocadas em casa de nebulização, por 45 dias. A aplicação de 300mg L-1 de 2,6-DHAP antes da aplicação de 200mg L-1 de AIB em estacas de 'Okinawa' proporcionou aumentos nos resultados das características de maior relevância para a propagação por estacas e pode ser uma técnica interessante para a estaquia em pessegueiro.

Novel neutral iron(II) isocyanide maleonitrile dithiolate [Fe(S2C2(CN)2)(t-BuNC) 4] compound

FeBr2 reacts with the S2C2(CN)2(2-) ion (1:1 ratio) in the presence of an excess of t-BuNC in THF to give the mixed ligand [Fe(S2C2(CN)2)(t-BuNC) 4] compound. This neutral product with a formal oxidation state of two for the iron atom was characterized by conductivity measurements, and, i.r., Mössbauer, 13C and ¹H n.m.r. spectroscopy. There is a Fe-C pi back-donation strengthened towards isocyanide ligands, according to the data of 13C, ¹H n.m.r. and Mössbauer spectroscopy.

Utilização do TEMPO (N-oxil-2,2,6,6-tetrametilpiperidina) na oxidação de álcoois primários e secundários

The oxidation of alcohols to obtain ketones, aldehydes or carboxylic acids is a fundamental transformation in organic synthesis and many reagents are known for these conversions. However, there is still a demand for mild and selective reagents for the oxidation of alcohols in the presence of other functional groups. As an alternative, the nitroxyl radical TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl) has been demonstrated to be a useful reagent for the transformation of alcohols. The oxidation of alcohols using TEMPO is often efficient, fast, selective, made in mild conditions and can tolerate sensitive functional groups. In this article we report different methodologies using TEMPO in the oxidation of alcohols.

Determination of traces of nitrate in water samples using spectrophotometric method after its preconcentration on microcrystalline naphthalene

Nitrate is quantitatively retained with 2,6-bis(4-methoxyphenyl)-4-phenyl pyrylium perchlorate (PPP) on microcrystalline naphthalene in the pH range of 6.5-9.0 from a large volume of aqueous solutions of various samples. The method was based on the complexation between PPP and nitrate and then, extraction of the resulted complex from aqueous solution by microcrystalline naphthalene. The solid mass consisting of the nitrate complex and naphthalene was then dissolved in dimethyl formamide (DMF) and absorption of the resulted solution was obtained at 328 nm. The linear calibration range for the determination of nitrate was 15-135 μg L-1 with the detection limit of 10 μg L-1.

Magnetic, thermal and spectral characterization of 2,6-dimethoxybenzoates of Co(II), Ni(II) and Cu(II)

The complexes of 2,6-dimethoxybenzoic acid anion with ions of Co(II), Ni(II), and Cu(II) have been synthesized as polycrystalline solids, and characterized by elemental analysis, spectroscopy, magnetic studies, and also by X-ray diffraction and thermogravimetric measurements. The analysed complexes have following colours: pink for Co(II), green for Ni(II), and blue for Cu(II) compounds. The carboxylate group binds as monodentate, and bidentate bridging and chelating ligands. On heating in air to 1173 K the complexes decompose in four, three or two steps. At first, they dehydrate in one or two steps to anhydrous salts, that next decompose to oxides of the respective metals. The solubility of the investigated dimethoxybenzoates in water at 293 K is of the order of 10-2 mol/dm3. Their magnetic moments were determined in the temperature range of 76-303 K. The results reveal the compounds of Co(II) and Ni(II) to be high-spin complexes and that of Cu(II) to form dimer.

Comparison of some properties of Cu(II) 2,3- , 3,5- and 2,6-dimethoxybenzoates

The physico-chemical properties and thermal stability in air of Cu(II) 2,3- , 3,5- and 2,6-dimethoxybenzoates were compared and the influence of the position of -OCH3 substituent on their thermal stability was investigated. The complexes are crystalline, hydrated salts with blue colour. The carboxylate ion is a bidentate chelating or bridging group. The thermal stability of analysed Cu(II) dimethoxybenzoates was studied in the temperature range of 293-1173 K. The positions of methoxy- groups in benzene ring influence the thermal properties of studied complexes. Their different thermal properties are markedly connected with the various influence of inductive, mesomeric and steric effects of -OCH3 substituent on the electron density in benzene ring. The magnetic susceptibilities of the complexes were measured over the range of 76-300 K and the magnetic moments were calculated. The results show that they form dimers.