Three molecular hybrids containing 1,4-naphthoquinones, 1,3,5-triazines, morpholine and 7-chloroquinoline, which have recognized contributions to the biological activity of many drugs, were synthesized in yields ranging from 43-84%. All hybrids were obtained in three steps starting from readily available reactants: lawsone, cyanuric chloride, morpholine and 4,7-dichloroquinoline. A previous docking study was carried out to identify the binding energy and pharmacophore conformation of the promising anticancer compounds with PI3Kγ (phosphoinositide 3-kinase) and AMPK (5’ AMP-activated protein kinase). The cancer activity in human metastatic melanoma cells (SKMEL-103) were performed, and the synthetized compounds presented half maximal inhibitory concentration (IC50) values around 25 µM. The expressions of PI3K and AMPK were also determined using western blotting technique, and all molecular hybrids negatively modulated both targets.

Hydroxynaphthoquinones such as lawsone (2-hydroxy-1,4-naphthoquinone) have proven to be effective antifungal agents. These compounds were tested for antifungal activity against yeast standard and clinical strains by the broth microdilution method. Among the synthetic lawsone derivatives, 2-hydroxy-3-((2-hydroxyphenyl)(pyrrolidin-1-yl)methyl)naphthalene-1,4-dione, 2-hydroxy-3-(((4-nitrophenyl)amino)(phenyl)methyl)naphthalene-1,4-dione and 2-hydroxy-3-((2-hydroxyphenyl)((4-nitrophenyl)amino)methyl)naphthalene-1,4-dione showed high activity against Candida albicans ATCC 10231, with minimal inhibitory concentrations (MICs) and minimal fungicidal concentrations (MFCs) ranging from 20 to 330 and from 80 to 330 µg mL-1, respectively. Moreover, they also showed a mechanism of action on exogenous ergosterol. Therapeutic concentrations (CC50) of 2-hydroxy-3-((2-hydroxyphenyl)(pyrrolidin-1-yl)methyl)naphthalene-1,4-dione, 2-hydroxy-3-(((4-nitrophenyl)amino)(phenyl)methyl)naphthalene-1,4-dione and 2-hydroxy-3-((2-hydroxyphenyl)((4-nitrophenyl)amino)methyl)naphthalene-1,4-dione were 52.81, 52.58 and 85.94 µg mL-1, respectively, which can be considered moderate or low. In addition, docking studies showed that these compounds had similar binding energy to standard ketoconazole, which are recognized as the molecular target by van der Waals interactions. Furthermore, they are under Lipinski's rule of 5 with a druglikeness score better than ketoconazole and nystatin. These findings suggest that 2-hydroxy-3-((2-hydroxyphenyl)(pyrrolidin-1-yl)methyl)naphthalene-1,4-dione, 2-hydroxy-3-(((4-nitrophenyl)amino)(phenyl)methyl)naphthalene-1,4-dione and 2-hydroxy-3-((2-hydroxyphenyl)((4-nitrophenyl)amino)methyl)naphthalene-1,4-dione have potential as leading compounds against human fungal infections.

In this study, we report the preparation of a new tetra-substituted epoxide aldehyde cyclopentane, which acts as a starting material for the synthesis of plinol, from (R)-(+)-epoxy-limonene. The synthesis was performed in three steps and resulted in a good yield. The structural determination was performed by 1H and 13C NMR, and the relative stereochemistry was defined by nuclear Overhauser effect (NOE) experiments with computer calculations of molecular modeling, particularly with respect to indirect coupling constant calculations.

Eleven 2,3-(substituted)-1,4-naphthoquinone derivatives were synthesized in yields ranging from 52-89%. These derivatives were evaluated for their cytotoxic effects on human lungs (H460), triple-negative breast (MDA-MB-231) and ovarian (A2780) cancer cell lines. Compounds 5f and 8 showed IC50values of 3.048 × 10-5 mol L-1 and 4.24 × 10-6 mol L-1 for H460; 5c and 8showed IC50 values of 2.16 × 10-5 mol L-1 and 1.60 × 10-5 mol L-1 for MDA-MB-231, and 5gand 8 showed IC50 values of 2.68 × 10-6 mol L-1 and 3.89 × 10-6 mol L-1 for A2780. Additionally, we conducted a docking study with the four most active compounds and the therapeutic targets PI3K and topoisomerase II showing the pharmacophoric conformation of these compounds.

A esterificação direta de naftoquinonas mostrou-se uma tarefa difícil. Metodologias mais comuns envolvem a aplicação de cloretos de acila em piridina ou anidridos, entretanto, quando ácidos de cadeia longa são utilizados tais metodologias se mostram ineficientes devido aos baixos rendimentos obtidos. Apresentamos uma nova síntese de ésteres de cadeia longa de juglona baseado na esterificação de Steglich utilizando um ácido de Lewis barato como cocatalisador. Rendimentos obtidos são consideravelmente maiores do que os reportados previamente. Química computacional foi utilizada para avaliar os efeitos do CeCl3 como cocatalisador. Os compostos preparados foram testados como inibidores de deposição de parafinas em petróleo. Éster palmítico da juglona foi capaz de reduzir 4 ºC na temperatura de início de aparecimento de cristais (WAT) do óleo estudado, representando uma redução de 1,5% m/m de parafinas normais precipitadas.

Direct esterification on naphthoquinone presented itself as a hard task. Usual methodologies apply acyl chloride in pyridine or anhydrides but with long-chain esters this procedure proved to be ineffective because of the low yields obtained. We present a new synthesis of long-chain esters of juglone based on Steglich esterification using a cheap Lewis acid as cocatalyst. Yields obtained are considerably better than those found previously. Computational chemistry was used to evaluate the effects of CeCl3 as cocatalyst. Prepared compounds were tested as wax deposition inhibitors in crude oil. Palmitic ester of juglone was able to lower 4 ºC on the wax appearance temperature (WAT) of the studied oil, representing a reduction of precipitated normal paraffin of 1.5% m/m.

De acordo com a literatura, a reação de Diels-Alder de furano sem uso de catalisador pode durar várias semanas e apresenta baixo rendimento devido à baixa reatividade do dieno. O uso de catalisadores ácidos de Lewis ou de altas pressões são descritos como métodos eficazes para melhorar o rendimento da reação. Este trabalho descreve nosso estudo recente sobre a utilização de pentacloreto de nióbio, como catalisador em reações de Diels-Alder entre furano e alguns dienófilos reativos, entre os quais o acrilato de metila apresentou bons rendimentos, especialmente sob temperaturas mais baixas. Outros dienófilos apresentaram rendimentos mais baixos devido a problemas, tais como a formação de produtos secundários e de elevado caráter de reversibilidade da reação.

According to the relevant literature, the Diels-Alder reaction of furan without a catalyst can last several weeks and shows a low yield due to the diene's low reactivity. The use of Lewis acid catalysts or high pressures is described as an effective method for improving the reaction yields. This paper describes our recent study on the use of niobium pentachloride as the catalyst in Diels-Alder reactions between furan and several reactive dienophiles, among which methyl acrylate showed good yields, especially at lower temperatures. Other dienophiles have shown lower yields because of problems such as byproduct formation and the high reversibility of the reaction.

To choose among the variety of oleaginous plants for biodiesel production, the oil content of several matrices was determined through different low-field ¹H nuclear magnetic resonance (NMR) experiments with varied pulse sequences, namely single-pulse, spin-echo, CPMG, and CWFP. The experiments that involved the first three sequences showed high correlation with each other and with the solvent extraction method. The quality of the vegetable oils was also evaluated on the basis of the existing correlation between the T2 values of the oils and their properties, such as viscosity, iodine index, and cetane index. These analyses were performed using HCA and PCA chemometric tools. The results were sufficiently significant to allow separation of the oleaginous matrices according to their quality. Thus, the low-field ¹H NMR technique was confirmed as an important tool to aid in the selection of oleaginous matrices for biodiesel production.

Uma série de novas Bases de Mannich (HL1-HL13) derivadas da 2-hidroxi-1,4-naftoquinona (lausona), benzaldeídos substituídos [C6H2R¹R²R³C(O)H] e várias aminas primárias (NH2R4, R4 = n-butil, benzil, alil, 2-furfuril) e seus complexos de Cu2+, [Cu(L1)2]-[Cu(L13)2], foram sintetizados e caracterizados por métodos analíticos e espectroscópicos. As estruturas dos complexos 1(R¹ = R² = R³ = H; R4 = Bu), 2(R¹ = R³ = H; R² = NO2; R4= Bu) e 7(R¹ = OH; R² = R³ = H; R4= Bu) foram determinadas por estudos de difração de raios-X de monocristal. Todos os compostos cristalizam em grupos espaciais centrossimétricos, com um cobre no centro de inversão. Dois L- coordenam-se através dos átomos de oxigênio do naftalen-2-olato e do nitrogênio da amina secundária, formando anéis quelatos de seis membros ao redor do átomo de cobre em um ambiente trans-N2O2. A atividade antimicrobial de todos os compostos foi testada em sete diferentes linhagens de bactérias: Bacillus cereus, Bacillus subtilis, Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosae Staphylococcus aureus. Em geral, as bases de Mannich foram mais ativas que os complexos, sendo HL11(R¹ = OH; R² =H; R³ = Me; R4= Bn) e HL13(R¹ = OH; R² = H; R³ = Br; R4= Bn) os inibidores mais potentes. O MIC para o composto mais ativo HL11contra S. Colifoi 20 µmol L-1 (8 µg mL-1), melhor que o cloranfenicol (90 µmol L-1) e bem abaixo da maioria dos valores descritos para outras naftoquinonas.

A series of novel Mannich bases (HL1-HL13) derived from 2-hydroxy-1,4-naphthoquinone (lawsone), substituted benzaldehydes [C6H2R¹R²R³C(O)H] and various primary amines (NH2R4, R4 = n-butyl, benzyl, allyl, 2-furfuryl), and their Cu2+ complexes, [Cu(L1)2]-[Cu(L13)2], have been synthesized and fully characterized by analytical and spectroscopic methods. The structures of complexes 1(R¹ = R² = R³ = H; R4 = Bu), 2(R¹ = R³ = H; R² = NO2; R4= Bu) and 7 (R¹ = OH; R² = R³ = H; R4= Bu) were determined by single crystal X-ray diffraction studies. All complexes crystallize in centrosymmetric space groups, with a copper atom in the inversion centre. Two L- coordinate through the naphthalen-2-olate oxygen and secondary amine-N atoms, forming six-membered chelate rings around the copper atom in a trans-N2O2 environment; spectroscopic data confirm that the other complexes exhibit similar molecular arrangement. The antimicrobial activity of all compounds has been tested on seven different strains of bacteria: Bacillus cereus, Bacillus subtilis, Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosaand Staphylococcus aureus. In general, Mannich bases were more active than complexes, HL11(R¹ = OH; R² =H; R³ = Me; R4= Bn) and HL13(R¹ = OH; R² = H; R³ = Br; R4= Bn) being the most potent inhibitors. The MIC for the most active compound HL11against S. Coliwas 20 µmol L-1 (8 µg mL-1), better than Chloramphenicol (90 µmol L-1) and well below most values reported for other naphthoquinones.