This study investigates the mechanisms of interaction between benzophenone derivatives and cruzain and Llacys1 (the protein expressed by cysteine protease gene isoform 1 of L. amazonensis) by homology modelling, docking and molecular dynamics simulation. The results predict that the same binding site in cruzain and Llacys1 is involved in complexes with benzophenone derivatives that cause non-competitive inhibition of the enzymes. The Gln residue is conserved among the enzymes, and is shown to be a key residue in the allosteric site of these cysteine proteases and in the interaction with benzophenone derivatives. The binding free energies highlight that the main energetic term contributing to the cruzain- and Llacys1-benzophenone compound interactions is the van der Waals term. Experimental results showed that benzophenone derivatives are promising potential inhibitors of cysteine proteases. Moreover, we found that two benzophenone derivatives are the most effective inhibitors of cruzain and L. amazonensis cysteine protease.

Dando continuidade as pesquisas de identificação de metabólitos secundários com propriedades anti-infecciosas potenciais a partir de espécies de plantas dos biomas brasileiros, dois alcaloides piperidínicos ( - )-cassina e ( - )-espectalina foram isolados das flores de Senna spectabilis (sin. Cassia spectabilis). As estruturas destes compostos foram elucidadas a partir de dados espectroscópicos e espectrométricos. Adicionalmente, esses alcaloides foram acetilados, resultando nos derivados ( - )-3-O-acetilcassina e ( - )-3-O-acetilespectalina. Todas as substâncias foram submetidas ao bioensaio empregando culturas de eritrócitos, infectadas com Plasmodium falciparum, um teste específico para avaliação antimalárica. Dentre as substâncias avaliadas, os dois primeiros alcaloides (IC50 1,82 µM e IC50 2,76 µM) foram mais potentes que os derivados (IC50 24,47 µM e IC50 25,14 µM) em comparação com a cloroquina (IC50 0,30 µM), utilizada como padrão. Estes dados mostram que os alcaloides piperidínicos constituem uma classe de produtos naturais que apresenta amplo espectro de atividades biológicas, sendo portanto, importantes modelos para o planejamento de fármacos, incluindo os antimaláricos.

In our continuing work looking for new anti-infective lead compounds from Brazilian biomes, the two known piperidine alkaloids ( - )-cassine and ( - )-spectaline were isolated from the flowers of Senna spectabilis (syn. Cassia spectabilis). Their structures were elucidated using a combination of spectroscopic and spectrometric data analysis. Further, these compounds were acetylated yielding the derivatives ( - )-3-O-acetylcassine and ( - )-3-O-acetylspectaline. All compounds were screened against P. falciparum-infected red blood cells (RBC) in culture, aiming to identify antimalarial prototypes. Among all compounds screened, the first two alkaloids (IC50 1.82 µM and IC50 2.76 µM) were more effective than the derivatives (IC50 24.47 µM and IC50 25.14 µM) in comparison to the standard compound chloroquine (IC50 0.30 µM). These data show that piperidine alkaloids constitute a class of natural products that feature a broad spectrum of biological activities, and are, therefore, important templates for drug design, including antimalarial.

O estudo fitoquímico das flores e frutos verdes de Senna spectabilis forneceu um novo alcaloide 2,6-dialquilpiperidin-3-ol chamado de (-)-7-hidróxi-cassina, juntamente com cinco alcaloides conhecidos: (-)-cassina, (-)-espectalina, (-)-3-O-acetil-espectalina, (-)-7-hidróxi-espectalina e (-)-6-iso-espectalina. Além dos alcaloides, também foram isolados constituintes químicos de outras classes como o esteroide β-sitosterol, os flavonoides luteolina e 3-metóxi-luteolina, o triterpeno ácido betulínico e o ácido trans-cinâmico. A partir do levantamento bibliográfico foi possível observar que os compostos estão sendo relatados pela primeira vez nesta espécie.

The phytochemical study of flowers and green fruits of Senna spectabilis furnished a new substituted 2,6-dialkylpiperidin-3-ol alkaloid, named (-)-7-hydroxycassine, along with five known piperidine alkaloids: (-)-cassine, (-)-spectaline, (-)-3-O-acetylspectaline, (-)-7-hydroxyspectaline and (-)-iso-6-spectaline. In addition to non-alkaloidal, chemical constituents from other chemical classes were also identified, including the steroid β-sitosterol, the flavonoids luteolin and 3-methoxyluteolin, the triterpene betulinic acid and trans-cinnamic acid. To our knowledge, compounds are being reported for the first time in this species.

Species of Cassia are widely distributed in tropical and subtropical regions throughout the world, and have been extensively investigated chemically and pharmacologically.They are known to be a rich source of phenolic derivatives, most of them with important biological and pharmacological properties. Some Asian, African and Indian tribes use these species as a laxative, purgative, antimicrobial, antipyretic, antiviral and anti-inflammatory agent. Among a number of other classes of secondary metabolites, such as anthracene derivatives, antraquinones, steroids and stilbenoids, biologically active piperidine alkaloids are an especially important bioactive class of compounds that showed to be restricted to a small group of Cassia species. In this paper we present an overview of the chemical, biological and ethnopharmacological data on Cassia piblished in the literature.

Alzheimer's disease (AD) is a progressive neurodegenerative pathology with severe economic and social impact. There is currently no cure, although cholinesterase inhibitors provide effective temporary relief of symptoms in some patients. Nowadays drug research and development are based on the cholinergic hypothesis that supports the cognition improvement by regulation of the synthesis and release of acetylcholine in the brain. There are only four commercial medicines approved for treatment of AD and natural products have played an important role in the research for new acetylcholinesterase inhibitors.

Many substances from different sources have been used by men for decades to control insects. After the 2nd World War, the use of inorganic compounds have declined drastically and natural products, as well as synthetic derivatives, have been widely used instead. The search for natural alternatives have improved the development of bench top bioassays and an array of synthetic approaches for known and novel natural products that shows relevant activities as feeding supressors and deterrents. The studies concerning mode of action and environmental impact of these substances, that may be biodegradable and selective for undesired insects, had led to the evaluation and discovery of a number of molecules, mostly terpenoids and alkaloids, that are well reported as candidates for inseticidal compounds that could be an effective alternative for insects control with a lower impact on human health, household animals and the environment.