Abstract Klebsiella pneumoniae is a species of Gram-negative bacteria related to a wide range of infections and high rates of drug resistance. The combined use of antibacterial agents is one of the strategies that has been analyzed in recent years as part of the alternatives in the treatment of drug-resistant infections. Recently, the antibacterial activity of of 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide has been demonstrated against K. pneumoniae, also indicating that this acetamide did not show significant cytotoxic potential in preliminary tests. Thus, it becomes an interesting substance for future studies that explore its antimicrobial capacity, including investigating its association with antibacterial drugs. Based on this, this research aimed to analyze the effects of the association of 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide (CFA) with ciprofloxacin, cefepime, ceftazidime, meropenem and imipenem against K. pneumoniae strains. The results showed additivity when the substance was combined with ciprofloxacin and cefepime, indifference when associated with ceftazidime and synergistic effect when combined with meropenem and imipenem. Thus, the acetamide was able to optimize the effects of antibacterial drugs, reducing the concentrations necessary to cause bacterial death. These data indicate a potential future clinical use of these combinations, and further studies are needed to analyze this viability.

This study describes a virtual screening performed for two series of selenides (28 compounds), derived from N-phenylacetamides chlorides and 7-chloro-quinoline, to determine their potential for leishmanicidal activity against Leishmania amazonensis and Leishmania donovani. Seven compounds were predicted as potential leishmanicides; therefore, they were synthesized from elemental selenium, as a precursor for the production of NaHSe, and subsequent reactions with 4,7-dichloro-quinoline and N-phenylacetamides chlorides were performed. The compounds were characterized by infrared (IR), 1H and 13C nuclear magnetic resonance (NMR), and sent for in vitro cytotoxicity tests against L. amazonensis and were found to be active and selective, and two compounds presented half-maximal inhibitory concentrations (IC50) of 5.67 and 10.81 µg mL-1. They also presented good interaction energies in the docking study, suggesting that may exert their effects by inhibiting the N-myristoyltransferase and O-acetylserine sulfhydrylase enzymes in parasites.

Abstract Aspergillus genus causes many diseases, and the species Aspergillus flavus is highly virulent. Treatment of aspergillosis involves azole derivatives such as voriconazole and polyenes such as amphotericin B. Due to an increase in fungal resistance, treatments are now less effective; the search for new compounds with promising antifungal activity has gained importance. The aims of this study were to evaluate the effects of the synthetic amide 2-chloro-N-phenylacetamide (A1Cl) against strains of Aspergillus flavus and to elucidate its mechanism of action. Thus, the minimum inhibitory concentration, minimum fungicidal concentration, conidial germination, associations with antifungal agents, cell wall activities, membrane activities and molecular docking were evaluated. A1Cl presented antifungal activity against Aspergillus flavus strains with a minimum inhibitory concentration of between 16 and 256 μg/mL and a minimum fungicidal concentration between 32 and 512 μg/mL. The minimum inhibitory concentration of A1Cl also inhibited conidial germination, but when associated with amphotericin B and voriconazole, it promoted antagonistic effects. Binding to ergosterol on the fungal plasma membrane is the likely mechanism of action, along with possible inhibition of DNA synthesis through the inhibition of thymidylate synthase. It is concluded that the amide 2-chloro-N-phenylacetamide has promising antifungal potential.

A series of fifteen new piperine-derived diesters was synthesized through the substitution reaction between the salt of piperic acid, obtained through piperine basic hydrolysis, with the δ-chloro-esters, obtained through the cleavage of tetrahydrofuran (THF) with acyl chlorides in the presence of ZnCl2. The final compounds were obtained with yields ranging from 50 to 84% and were characterized by infrared (IR) and 1H and 13C nuclear magnetic resonance spectroscopy (NMR). The new compounds were evaluated in silico in regard to their ADME (absorption, distribution, metabolism, and excretion) properties, and in vitro for their antimicrobial activity against bacteria strains (Staphylococcus aureus and Pseudomonas aeruginosas), yeast fungi (Candida albicans and C. tropicalis) and filamentous fungi (Aspergillus fumigatus, A. flavus and A. niger). The results from the in silico studies of Lipinski’s rule of five showed that most compounds present good pharmacological possibilities, and the results from in vitro antimicrobial activity showed that 8 of the 15 synthesized compounds displayed antimicrobial activity, inhibiting the growth of 40-80% of tested strains, with a minimum inhibitory concentration (MIC) interval ranging from 1024 to 256 µg mL−1.

This work aims to investigate the energy-related characteristics of apple bagasse, orange bagasse and cashew-apple bagasse to identify their potential as bioenergy feedstocks. For this, a detailed characterization was performed, including proximate analysis, ultimate analysis, atomic molar ratio, heating values, chemical composition, bulk density, bioenergy density, fuel-value-index (FVI), fossil fuel equivalence and potential CO2 retention. Proximate composition revealed moisture, volatile matter, fixed carbon and ash contents in the range of 7.8-9.3%, 67.1-74.2%, 16.2-22.0% and 1.6-5.7%, respectively. Typical values for carbon (44.8-49.9 wt.%), hydrogen (5.5-6.6 wt.%) and oxygen (40.1-44.2 wt.%), with low sulfur (< 0.1 wt.%) and nitrogen (< 2.7 wt.%) contents were found. In regard to bulk density (237.7-554 kg m−3) and bioenergy density (3.93-10.1 GJ m−3), juice processing residues have substantial values when compared with well-known lignocellulosic residues. Recoverable energy potential from the juice processing residues varied from 15.24 to 17.03 MJ kg−1. From FVI analysis, apple bagasse is expected to be more suitable for thermochemical processing. Orange bagasse, on the other hand, has the highest equivalent in fossil fuel volume. Consequently, its use as solid fuel may lead to a decrease in CO2 emissions from reference fuels.

Piperine, previously extracted from black pepper (Piper nigrum L.), was used as a precursor for the synthesis of twelve new diester derivatives. The final products were obtained through the bimolecular nucleophilic substitution reaction (SN2) of the alkyl 2-chloroacetates and the salt of piperic acid, obtained from the basic hydrolysis of piperine. The compounds were synthesized with yields of 55-84% and characterized by infrared spectroscopy and 1H and 13C nuclear magnetic resonance. The evaluation of the compounds’ potential as new drug candidates was done through an in silico study of ADME properties (absorption, distribution, metabolization and excretion) and evaluation of antimicrobial activity against bacterial strains (Staphylococcus aureus and Pseudomonas aeruginosa), yeasts (Candida albicans and Candida tropicalis) and filamentous fungi (Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger). The in silico study showed that the compounds were good drug candidates and antimicrobial evaluation demonstrated that 9 of the 12 compounds exhibited a minimum inhibitory concentration (MIC) ranging 1024-256 μg mL-1.

New diesters derived from phthaloylglycine (7a-7i) were synthesized and their structures characterized by infrared, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. The compounds were evaluated in an in silico study, which demonstrated positive features indicating a possible drug candidate. The diesters showed antifungal activity ranging from moderate to strong against strains of Candida. Compounds 7a, 7b, 7c, 7e and 7i had a moderate minimum inhibitory concentration (MIC) of 1024 µg mL−1 against all fungal strains, while 7h showed a very good MIC of 256 µg mL−1 against Candida albicans, Candida parapsilosis and Candida krusei and 64 µg mL−1 against Candida tropicalis. However, only 7h and 7i were able to inhibit bacterial growth of strains of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Escherichia coli with an MIC of 1024 µg mL−1.

Nine new compounds derived from selenoglycolic acid were synthesized, and their structures were fully characterized by elemental analysis, infrared (IR), 1H and 13C nuclear magnetic resonance (NMR). The compounds were evaluated in an in silico study and showed strong to moderate antibacterial activity against several strains of Staphylococcus aureus. In particular, three compounds exhibited excellent antibacterial activity, with minimum inhibitory concentrations (MICs) between 16 and 64 µg mL-1. Furthermore, two of the nine compounds showed antifungal activity, with MIC of 1024 and 512 µg mL-1. In silico studies of the parameters of Lipinski's rule of five indicate that these compounds have potential to be new drug candidates.

A series of ten new compounds have been synthetized in satisfactory yields (85-95%) through the treatment of isopropyl mesoionic 1,3-thiazolium-5-thiolate with 2-chloro-N-arylacetamides and characterized by elemental analysis, infrared (IR), 1H and 13C nuclear magnetic resonance (NMR) spectroscopies. The newly synthesized compounds were evaluated as new drug candidates in in silico study and for their antifungal activity against several strains of Candida albicans. In silico study indicates that no compound has potential to be a new drug while four compounds showed medium to strong activity with minimum inhibitory concentration (MIC) range of 256-1024 µg mL-1.

Uma série de 21 derivados, 1,3,4-oxadiazolinas, foi sintetizada pela ciclização de N-acilhidrazonas com anidrido acético e avaliada in vitro quanto à sua atividade antifúngica contra seis espécies de Candida: Candida albicans (ATCC 90028 e LM V-42), Candida krusei (ATCC 6258 e LM 12 C) e Candida tropicalis (ATCC 13803 e LM 14). As espécies de Candida foram consideradas sensíveis a uma série dos compostos, os quais inibiram o crescimento de 50 a 90%, com um intervalo de concentração inibitória mínima (MIC) de 64 a 512 µg mL-1. As estruturas dos compostos foram totalmente confirmadas e caracterizadas pelas técnicas de infravermelho com transformada de Fourier (FTIR), ressonância magnética nuclear (NMR) de ¹H e 13C, e espectrometria de massa (MS).

A series of 21 1,3,4-oxadiazoline derivatives was synthesized by cyclization of N-acylhydrazones with acetic anhydride and evaluated for their in vitro antifungal activity against six Candida strains: Candida albicans (ATCC 90028 and LM V-42), C. krusei (ATCC 6258 and LM 12 C) and C. tropicalis (ATCC 13803 and LM 14). The Candida strains were found to be sensitive to some of the compounds, which inhibited the growth by 50-90%, with minimum inhibitory concentration (MIC) in the range of 64-512 µg mL-1. The compounds' structures were fully confirmed and characterized by Fourier transform infrared spectroscopy (FTIR), ¹H and 13C nuclear magnetic resonance (NMR) and mass spectrometry (MS).

Cálculos semi-empíricos do tipo AM1-TDHF para a primeira hiperpolarizabilidade estática, β(0), de dezesseis compostos mesoiônicos do sistema 1,3-tiazólio-5-tiolato foram realizados. Com base nos resultados obtidos, dois novos compostos mesoiônicos, 2-(4-nitrofenil)-3-metil-4-(metilfenil)-1,3-tiazólio-5-tiolato e 2-(4-nitrofenil)-3-metil-4-(metoxifenil)-1,3-tiazólio-5-tiolato, foram sintetizados e caracterizados por métodos espectroscópicos e analíticos.

Semiempirical AM1-TDHF calculations of the static first hyperpolarizabilities, β(0), of 1,3-thiazolium-5-thiolate mesoionic derivatives were performed. Guided by these results, two new mesoionic compounds - 2-(4-nitrophenyl)-3-methyl-4-(methylphenyl)-1,3-thiazolium-5-thiolate and 2-(4-nitrophenyl)-3-methyl-4-(methoxyphenyl)-1,3-thiazolium-5-thiolate - were synthesized and characterized by analytical and spectroscopic means.

Cerca de um terço dos pacientes epilépticos não conseguem ter um tratamento adequado com as drogas anticonvulsivantes atuais. Nesse sentido, as plantas medicinais surgem como uma fonte promissora de novas moléculas químicas com propriedades biológicas apreciáveis. Muitas plantas ou produtos de origem naturais têm sido propostos para o tratamento de várias patologias, tais como: epilepsia, diabetes, ansiedade, depressão, dentre outras. O presente trabalho realizou um extenso levantamento na literatura especializada de plantas medicinais com propriedades anticonvulsivantes. Um total de 355 espécies vegetais foi identificado, sendo 16 plantas encontradas na flora brasileira, com indicação para o tratamento de quadros convulsivos. Características como nome da espécie, família, partes utilizadas, país do estudo e /ou publicação, métodos e referências foram sumarizados. Além disso, os principais apectos dos modelos animais mais utilizados no estudo de plantas/substâncias com propriedades anticonvulsivantes foram revisados. Mais de 170 referências foram consultadas.

Seizures are resistant to treatment with currently available anticonvulsant drugs in about 1 out of 3 patients with epilepsy. Thus, there is a need for new, more effective anticonvulsant drugs for intractable epilepsy. However, nature is a rich source of biological and chemical diversity and a number of plants in the world have been used in traditional medicine remedies, i.e., anticonvulsant, anxiolytic, analgesic, antidepressant. This work constitutes a literature review on medicinal plants showing anticonvulsant properties. The review refers to 16 Brazilian plants and a total 355 species, their families, geographical distribution, the utilized parts, method and references. Some aspects of research on medicinal plants and a brief review of the most common animal models to discover antiepileptic drugs are discussed. For this purpose over 170 references were consulted.

A hanseníase é uma doença crônica infecciosa ocasionada pelo Mycobacterium leprae. Foi considerada incurável por muitos anos. Atualmente a lepra é uma doença em desaparecimento, apesar de podermos encontrá-la principalmente nos países da zona tropical. O Brasil é o país que tem o segundo maior número de casos de lepra ao redor do mundo com quase 30.000 novos casos diagnosticados em 2005. Este trabalho teve como objetivo revisar a literatura dos vegetais e substâncias de origem natural com atividade antileprótica. Foram encontradas 11 plantas e 17 substâncias isoladas de plantas e microrganismos que foram classificados em grupos químicos adequados. Alguns aspectos de pesquisa recente com produtos naturais direcionados à produção de drogas contra a lepra também são discutidos. Foram consultadas 63 referências.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae bacillus. It was considered to be an incurable disease for ages. Nowadays leprosy is a vanishing disease although we can meet it principally in the tropical zone countries. Brazil has the second greatest number of leprosy cases around the world with almost 30,000 new cases diagnosed in 2005. The present work constitutes a literature review on plant extracts and chemically defined molecules of natural origin showing antileprotic activity. The review refers to 11 plants, their families, and geographical distribution, the utilized parts, the type of extract and the tested organism. It also includes 17 compounds isolated from higher plants and microorganisms, classified into appropriate chemical groups. Some aspects of recent antileprotic-activity-directed research on natural products are discussed. For this purpose 63 references were consulted.

Três novos alcalóides sesquiterpênicos do tipo guaiano, muscicapina A (1), muscicapina B (2) e muscicapina C (3) foram isolados das raízes de Croton muscicapa. As estruturas foram elucidadas através de análises espectroscópicas, principalmente RMN de 1D e 2D e espectrometria de massas. Este é o primeiro relato na literatura de uma nova classe de alcalóides sesquiterpênicos com esqueleto guaiano.

Three new guaiane-type sesquiterpene alkaloids, muscicapine A (1), muscicapine B (2), and muscicapine C (3) were isolated from the roots of Croton muscicapa. The structures were established by analysis of spectroscopic data, mainly 1D and 2D NMR and MS. This is the first report of a new class of guaiane-type sesquiterpene alkaloids.