Leishmania (Leishmania) amazonensis is a protozoan that causes infections with a broad spectrum of clinical manifestations. The currently available chemotherapeutic treatments present many problems, such as several adverse side effects and the development of resistant strains. Natural compounds have been investigated as potential antileishmanial agents, and the effects of epoxy-␣-lapachone on L. (L.) amazonensis were analyzed in the present study. This compound was able to cause measurable effects on promastigote and amastigote forms of the parasite, affecting plasma membrane organization and leading to death after 3 h of exposure. This compound also had an effect in experimentally infected BALB/c mice, causing reductions in paw lesions 6 weeks after treatment with 0.44 mM epoxy-␣-lapachone (mean lesion area, 24.9 ؎ 2.0 mm 2 ), compared to untreated animals (mean lesion area, 30.8 ؎ 2.6 mm 2 ) or animals treated with Glucantime (mean lesion area, 28.3 ؎ 1.5 mm 2 ). In addition, the effects of this compound on the serine proteinase activities of the parasite were evaluated. Serine proteinase-enriched fractions were extracted from both promastigotes and amastigotes and were shown to act on specific serine proteinase substrates and to be sensitive to classic serine proteinase inhibitors (phenylmethylsulfonyl fluoride, aprotinin, and antipain). These fractions were also affected by epoxy-␣-lapachone. Furthermore, in silico simulations indicated that epoxy-␣-lapachone can bind to oligopeptidase B (OPB) of L. (L.) amazonensis, a serine proteinase, in a manner similar to that of antipain, interacting with an S1 binding site. This evidence suggests that OPB may be a potential target for epoxy-␣-lapachone and, as such, may be related to the compound's effects on the parasite.

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Twenty-three naphthoimidazoles and six naphthoxazoles were synthesised and evaluated against susceptible and rifampicin- and isoniazid-resistant strains of Mycobacterium tuberculosis. Among all the compounds evaluated, fourteen presented MIC values in the range of 0.78 to 6.25 μg/mL against susceptible and resistant strains of M. tuberculosis. Five structures were solved by X-ray crystallographic analysis. These substances are promising antimycobacterial prototypes.

Herein we present a high-temperature/highpressure continuous flow synthesis of 1H-4-substituted imidazoles starting from α-bromoacetophenones and carboxylic acids. 1H-4-aryl imidazoles are key building blocks in the synthesis of NS5A inhibitors, including daclatasvir as the most prominent example. The reaction sequence started with the generation of the α-acyloxy ketone from α-bromoacetophenone and the carboxylic acid. The subsequent condensation to the 1H-4-substituted imidazole was performed with ammonium acetate in a high-temperature stainless steel coil reactor. High-temperature operation (> ∼ 150 °C) was essential for this reaction to form the desired imidazole in high purity. Intensification of chemical reactions in continuous flow reactors has emerged as key enabling technology for process enhancement and for reducing the environmental impact of chemical processes. The continuous flow setup allowed rapid heating of the reaction mixture to the desired temperature. Furthermore, operation at elevated pressure (∼17 bar) eliminated headspace and increased the concentration of volatile compounds in the liquid phase. The imidazole formation was completed in the coil reactor after residence times of only 2 to 5 min. The products were isolated after the two step reaction sequence in high purity by a simple extraction procedure. Imidazoles derived from chiral amino acids were obtained as the optically pure compounds.