The 1,4-naphthoquinones are an important group of compounds intensively studied because of their wide range of biological activities. Four 2-chloro-3-(substituted-phenylamino)-1,4 naphthoquinone derivatives were synthesized, and the vibrational modes of these molecules were assigned using Raman and Fourier transform infrared spectroscopy (FTIR) techniques. In addition, X-ray studies were performed for one of these derivatives. Density functional theory (DFT) calculations were also developed for these compounds and presented. In summary, the results obtained from these studies can assess chemical changes in the structures of functionalized quinones and the discovery of candidate biologically active compounds.

RESUMO: A intoxicação por Trema micrantha, comumente causa em bovinos, ovinos e caprinos necrose hepatocelular e, edema e hemorragia cerebral em equinos. Essa planta em ovinos pode causar pneumopatia tóxica, existindo descrição apenas de um relato da forma natural e um da forma experimental no estado do Rio Grande do Sul. O objetivo deste trabalho é relatar, um surto, da forma respiratória de intoxicação natural por T. micranta em ovinos. Seis ovinos desenvolveram sinais clínicos respiratórios após o consumo da planta e destes quatro morreram e dois após o tratamento com dexametasona se recuperaram. Os ovinos apresentaram taquipneia, respiração ruidosa, edema de face, pálpebras, vulva e enfisema subcutâneo na face e pescoço. Na necropsia (Ovinos 2, 3 e 4) observou-se pulmões não colabados, pesados, vermelhos difusos com impressões costais evidentes e ao corte fluindo moderada quantidade de líquido serosanguinolento. O fígado apresentava padrão lobular evidente difuso moderado. Na histopatologia, em pulmões dos três ovinos necropsiados havia congestão e edema com formação de membranas hialinas no interior de alvéolos difusos acentuados, além de espessamento dos septos alveolares devido a hiperplasia de pneumócitos tipo II difuso discreta à moderada, havia ainda, infiltrado de macrófagos, linfócitos, plasmócitos e neutrófilos difuso discreto a moderado no lúmen de alvéolo, brônquios e bronquíolos. No Ovino 3, observou-se ainda pneumócitos tipo II com núcleos aumentados e hipercromáticos, por vezes binucleados com nucléolos evidentes, e em algumas regiões estes pneumócitos estavam descamados para a luz alveolar formando pequenos sincícios e no epitélio de brônquios havia hiperplasia multifocal discreta. A avaliação IHQ anti-citoqueratina demonstrou marcação intracitoplasmática difusa acentuada em pneumócitos tipo II hiperplásicos no epitélio bronquiolar dos três ovinos avaliados. No fígado dos três ovinos havia necrose centrolobular multifocal discreta. Este parece ser o segundo relato da intoxicação espontânea por T. micrantha em ovinos desenvolvendo lesões pulmonares, descrito no Brasil e o primeiro no estado de Santa Catarina.

ABSTRACT: Poisoning by Trema micrantha commonly causes hepatocellular necrosis in cattle, sheep, and goats and edema and cerebral hemorrhage in horses. This plant can cause toxic pneumopathy in sheep, and there is only one report of the natural form and one of the experimental form in the State of Rio Grande do Sul. This study aimed to report an outbreak of the respiratory form of natural poisoning by T. micrantha in sheep. Six sheep developed clinical respiratory signs after consumption of the plant and four of them died and two recovered after treatment with dexamethasone. The sheep presented tachypnea, noisy breathing, edema of the face, eyelids, and vulva, and subcutaneous emphysema on the face and neck. Necropsy (Sheep 2, 3, and 4) showed uncollapsed, heavy, diffuse red lungs with evident costal impressions and a moderate amount of serosanguineous fluid flowed at section. The liver had a moderate diffuse evident lobular pattern. The histopathology of the lungs of the three necropsied sheep showed congestion and edema with the formation of hyaline membranes within accentuated diffuse alveoli, in addition to thickening of the alveolar septa due to mild to moderate diffuse type II pneumocyte hyperplasia and also mild to moderate diffuse infiltrate of macrophages, lymphocytes, plasma cells, and neutrophils in the lumen of alveoli, bronchi, and bronchioles. Sheep 3 also showed type II pneumocytes with enlarged and hyperchromatic nuclei, sometimes binucleated with evident nucleoli, and, in some regions, the pneumocytes were desquamated to the alveolar lumen forming small syncytia and mild multifocal hyperplasia in the bronchial epithelium. The anti-cytokeratin IHC evaluation showed marked diffuse intracytoplasmic staining in hyperplastic type II pneumocytes in the bronchiolar epithelium of the three evaluated sheep. The liver of the three sheep had mild multifocal centrilobular necrosis. It seems to be the second report of spontaneous poisoning by T. micrantha in sheep developing lung lesions described in Brazil and the first in the State of Santa Catarina.

In this work, we report the synthesis of three series of carbohydrate-based benzo[f]indole-4,9-diones and amino-1,4-naphthoquinone derivatives and evaluated their cytotoxic activity against eight human cancer cell lines. Several compounds showed a promising cytotoxic activity toward the tumor cell lines (half maximal inhibitory concentration (IC50) < 10.0 μM). The importance of the substitution pattern of the quinone derivatives on the antitumor activity was also discussed. 3-Carboethoxy-2-methyl-benzo[f]indole-4,9-dione derivatives were more cytotoxic than their parent compounds and amino-1,4-naphthoquinones. Unlike clinically useful anticancer agent doxorubicin, the majority of synthesized compounds did not exhibit any lytic effects against erythrocytes or normal human leukocytes.

We reported experimental and theoretical investigation of conformers of 1,2,3-triazole derivatives, substances of exclusively synthetic origin, subject of extensive studies, because of several biological properties, such as antiviral, antimicrobial and antileishmaniasis. We reported molecular/supramolecular X-ray structures of antiophidian compounds I and II. For I and II there are two crystallographic different molecules in the unit cell (A and B). To explore the causes of the similarities in the compound’s crystal structures, intermolecular interactions were explored using the Hirshfeld surface as the fingerprint plots. In addition, density functional theory (DFT) calculations were carried out at the ωB97x-D/6-31G(d,p)-PCM-CHCl3 level aiming to contribute to the interpretation of the experimental data and complement the experimental findings. Two structures named 2A and 5B were found in good agreement with the respective X-ray solid state ones (A and B). Theoretical 1H nuclear magnetic resonance (NMR) spectra calculated for 5B rotated structure (torsion angles deviation around 40° to 90°) was in fine agreement with experimental results (in CDCl3) indicating that the solution molecular structure is considerably different from optimized equilibrium geometries and solid-state structure. Therefore, care is needed when using X-ray structures or DFT geometries to model interaction of drugs with biological targets since significant conformational changes may take place in solution.

The aim of this paper was to revive the accurate determination of the boiling point of organic compounds using the percolator technique developed in the 1960s. Although this method is simple, fast and efficient it is omitted from current textbooks. This method has several advantages over Siwoloboff such as high reproducibility and direct measurement of the boiling point of the sample obtained by observing the temperature of the vapor-liquid equilibrium. The experiments were performed in the organic chemistry laboratory but allow interdisciplinary integration with other disciplines of several academic areas.

Neste trabalho nós descrevemos o uso do ultrassom na síntese de novas naftoquinonas, 6a-f e 7a-c, contendo na posição 2 do anel quinonoídico substituintes do tipo aminocarboidratos. Estas substâncias foram preparadas, em condições brandas, através da reação da 1,4-naftoquinona (8a) ou do metoxi-lapachol (8b) com diferentes aminocarboidratos 9a-d. As estruturas das substâncias foram confirmadas através das técnicas de RMN de ¹H e de 13C-APT, uni- e bi-dimensionais (COSY-¹H vs. ¹H e HETCOR ¹J CH), e por espectrometria de massas de alta resolução com ionização por electrospray (ESI MS).

In this report we describe the ultrasound-accelerated synthesis of new naphthoquinone derivatives 6a-f and 7a-c, which possess an aminocarbohydrate chain at the C-2 position of the quinone ring. This novel type of 1,4-naphthoquinone derivative has been synthesized under mild conditions by the reaction of 1,4-naphthoquinone (8a) or methoxylapachol (8b) with different aminocarbohydrates 9a-d. Characterization of all substances was confirmed by one- and two-dimensional nuclear magnetic resonance (NMR) techniques (¹H, 13C-APT, cosy-¹H vs. ¹H and HETCOR ¹J CH) and by high-resolution electrospray ionization mass spectrometry (HR ESI MS).

The aromatic six-membered heterocycles having three nitrogen atoms are denominated triazines. Among these heterocycles, isocyanuric chloride and cyanuric chloride are inexpensive and readily available 1,3,5-triazine derivatives, which have been attracting significant attention of organic chemists due to their different kinds of applications, which vary from pharmaceuticals to explosives. This short overview explores their uses in synthetic methods, as chlorinating and oxidating agents and some procedures for their preparation.

The 1,2,3-triazole, known since the end of 19th century, is a very widely used heterocyclic system present in many synthetic substances and commercial pharmaceutical compounds. In fact, 1,2,3-triazoles show several applications in many areas especially as medicines against many diseases like cancer, AIDS, Parkinson and Alzheimer. Nowadays there is a large variety of known methods to obtain these heterocyclic compounds comprising mainly three synthetic routes. Nevertheless, there is no article that gives an objective overview of the synthetic methods for obtaining these kinds of azoheterocycles. This paper presents a brief history of this class of compounds, and a synthetic discussion concerning the main synthetic methods for its preparation, such as cyclization through hydrazones, concerted cycloadditon [2+3] and pseudopericyclic cyclization - and some others of restricted application, but also important. Finally, this paper also provides a brief overview on pharmacological applications of some 1,2,3-triazoles.

Neste trabalho estão descritas as sínteses dos ribonucleosídeos pirrólicos reversos 5-C-(4-acetil-5-metil-pirrol-1-il)-2,3-O-isopropilideno-5-desoxi- beta-D-ribofuranosídeo de metila (10), 5-C-(4-etoxicarbonil-5-metil-pirrol-1-il)-2,3-O-isopropilideno-5-desoxi- beta-D-ribofuranosídeo de metila (11), 5-C-(4-acetil-5-metil-pirrol-1-il)-5-desoxi-beta-D-ribofuranosídeo de metila (12), 5-C-(4-etoxicarbonil-5-metil-pirrol-1-il)-5-desoxi- beta-D-ribofuranosídeo de metila (13), 5-desoxi-5-C-(3'-formil-4'-hidroxipropil-pirrol-1'-il)-2,3-O-isopropilideno- beta-D-ribofuranosídeo de metila (16) e 5-desoxi-5-C-(3'-formil-pirrol-1'-il)-2,3-O-isopropilideno- beta-D-ribofuranosídeo de metila (18) a partir do 5-amino-5-desoxi-2,3-O-isopropilideno-beta-D-ribofuranosídeo de metila (9), matéria-prima de fácil preparação. A estratégia sintética para a construção do anel heterocíclico baseou-se no ataque nucleofílico da amina 9 aos diidrofuranos: 4-acetil-2-n-butoxi-5-metil-4,5-diidrofurano (4), 4-carbetoxi-2-n-butoxi-5-metil-4,5-diidrofurano (5), 4-formil-2-n-butoxi-4,5-diidrofurano (6) e 4-formil-1-metil dioxabiciclo[3.3.0]oct-3-eno (8, in situ), obtidos através da reação dos diazo compostos 3-diazo-2,4-pentadiona (1), 2-diazoacetoacetato de etila (2) e diazomalonaldeído (3) com enol-éteres, sob catálise de tetraacetato de di-ródio.

The synthesis of reverse pyrrole ribonucleosides methyl 5-C-(4-acetyl-5-methyl-pyrrol-1-yl)-2,3-O-isopropylidene-5-deoxy- beta-D-ribofuranoside (10), methyl 5-C-(4-ethoxycarbonyl-5-methyl-pyrrol-1-yl)-2,3-O-isopropylidene-5-deoxy- beta-D-ribofuranoside (11), methyl 5-C-(4-acetyl-5-methyl-pyrrol-1-yl)-5-deoxy-beta-D-ribofuranoside (12), methyl 5-C-(4-ethoxycarbonyl-5-methyl-pyrrol-1-yl)-5-deoxy- beta-D-ribofuranoside (13), methyl 5-deoxy-5-C-(3'-formyl-4'-hydroxypropyl-pyrrol-1'-yl)-2,3-O-isopropylidene- beta-D-ribofuranoside (16) and methyl 5-deoxy-5-C-(3'-formyl-pyrrol-1'-yl)-2,3-O-isopropylidene- beta-D-ribofuranoside (18) are described starting from readily available methyl 5-amino-5-deoxy-2,3-O-isopropylidene-beta-D-ribofuranoside (9). The synthetic strategy for the construction of the heterocyclic ring was based on the nucleophilic attack of (9) to 4-acetyl-2-n-butoxy-5-methyl-4,5-dihydrofuran (4), 4-carbetoxy-2-n-butoxy-5-methyl-4,5-dihydrofuran (5), 4-formyl-2-n-butoxy-4,5-dihydrofuran (6) and 4-formyl-1-methyl dioxabyciclo[3.3.0]oct-3-en (8, in situ). The later compounds were obtained from reaction between 3-diazo-2,4-pentadione (1), ethyl 2-diazoacetoacetate (2) or diazomalonaldehyde (3) and enol ethers using dirhodium tetraacetate as a catalyst.

Diazocarbonyl compounds are a very important class of organic substances which have a long history of useful aplications in organic chemistry. The focus of this report deals with the use of diazocarbonyl compounds in a ariety of important reactions and their application in organic synthesis. These reactions are briefly summarized showing their broad scope.

Estudo prospectivo visando identificar e comparar que conhecimentos básicos relativos à leishmaniose visceral (LV) têm as populações com características distintas, residentes em áreas periurbanas (Maracanã instalação e ocorrência de casos de LV antigas; Vila Nova/Bom Viver instalação e ocorrência recentes) e rural, Município de Codó instalação antiga e ocorrência recentes. No período compreendido entre agosto de 1996 a janeiro de 1997, aplicou-se questionário com perguntas abertas e fechadas, sendo abordados aspectos referentes à epidemiologia, prevenção, clínica e terapêutica. A população de estudo foi formada pelos casos de LV registrados pela FNS/MA e seus vizinhos. Foram entrevistados os residentes de 283 casas: 53 do Maracanã; 103, em Vila Nova/Bom Viver; 127, em Codó. Foi referido ambiente favorável para o desenvolvimento e manutenção da doença. Do total dos entrevistados, 93,8%, percentual significativo, ouviram falar de LV, por meio de fontes não oficiais. No Maracanã, 50,9% referiram transmissão pelo mosquito; 87,2% reconheciam o envolvimento do cão na cadeia epidemiológica da doença. Os entrevistados estão cientes da gravidade do mal, sendo capazes de identificar casos suspeitos, humano ou canino. Medidas de controle são desconhecidas por 77,8%. Sete pessoas sabiam que o Glucantime® é usado no tratamento da LV. Concluiu-se que o nível de conhecimento sobre LV foi baixo, principalmente em relação à prevenção e à terapêutica, situação semelhantes nas três áreas.

A prospective study was performed to identify knowledge concerning visceral leishmaniasis (VL) in endemic areas of Maranhão, amongst the rural population of the Codó township and in a peripheral urban area (an old settlement, Maracanã, on the outskirts of the city of São Luís, and Vila Nova/Bom Viver, Paço do Lumiar township). A total of 283 persons were interviewed, including 53 from Maracanã, 103 from Vila Nova/Bom Viver, and 127 from Codó. The sites presented favorable conditions for the development and maintenance of VL. Some 93.8% of those interviewed had heard of kala-azar. In Maracanã, 50.9% referred to sandflies as responsible for the transmission of VL, while 87.2% knew that dogs are the main link in the epidemiological cycle of the disease. Some 77.8% of those interviewed did not know how to control the disease. As regards manifestations of the disease, they largely associated it with fever, anemia, weight loss, and an enlarged abdomen. Only five individuals knew that Glucantime® is used to treat VL. We conclude that knowledge is poor with regard to all aspects of VL in both the rural and peripheral urban area.

Estudo prospectivo visando identificar e comparar que conhecimentos básicos relativos à leishmaniose visceral (LV) têm as populações com características distintas, residentes em áreas periurbanas (Maracanã instalação e ocorrência de casos de LV antigas; Vila Nova/Bom Viver instalação e ocorrência recentes) e rural, Município de Codó instalação antiga e ocorrência recentes. No período compreendido entre agosto de 1996 a janeiro de 1997, aplicou-se questionário com perguntas abertas e fechadas, sendo abordados aspectos referentes à epidemiologia, prevenção, clínica e terapêutica. A população de estudo foi formada pelos casos de LV registrados pela FNS/MA e seus vizinhos. Foram entrevistados os residentes de 283 casas: 53 do Maracanã; 103, em Vila Nova/Bom Viver; 127, em Codó. Foi referido ambiente favorável para o desenvolvimento e manutenção da doença. Do total dos entrevistados, 93,8%, percentual significativo, ouviram falar de LV, por meio de fontes não oficiais. No Maracanã, 50,9% referiram transmissão pelo mosquito; 87,2% reconheciam o envolvimento do cão na cadeia epidemiológica da doença. Os entrevistados estão cientes da gravidade do mal, sendo capazes de identificar casos suspeitos, humano ou canino. Medidas de controle são desconhecidas por 77,8%. Sete pessoas sabiam que o Glucantime® é usado no tratamento da LV. Concluiu-se que o nível de conhecimento sobre LV foi baixo, principalmente em relação à prevenção e à terapêutica, situação semelhantes nas três áreas.

A prospective study was performed to identify knowledge concerning visceral leishmaniasis (VL) in endemic areas of Maranhão, amongst the rural population of the Codó township and in a peripheral urban area (an old settlement, Maracanã, on the outskirts of the city of São Luís, and Vila Nova/Bom Viver, Paço do Lumiar township). A total of 283 persons were interviewed, including 53 from Maracanã, 103 from Vila Nova/Bom Viver, and 127 from Codó. The sites presented favorable conditions for the development and maintenance of VL. Some 93.8% of those interviewed had heard of kala-azar. In Maracanã, 50.9% referred to sandflies as responsible for the transmission of VL, while 87.2% knew that dogs are the main link in the epidemiological cycle of the disease. Some 77.8% of those interviewed did not know how to control the disease. As regards manifestations of the disease, they largely associated it with fever, anemia, weight loss, and an enlarged abdomen. Only five individuals knew that Glucantime® is used to treat VL. We conclude that knowledge is poor with regard to all aspects of VL in both the rural and peripheral urban area.