Marco Edilson Freire de Lima

Studies on the effectiveness of diarylheptanoids derivatives against Leishmania amazonensis

In a previous work we demonstrated that diarylheptanoids extracted from Centrolobium sclerophyllum are very active against Leishmania amazonensis promastigotes. In order to continue our studies with these class of compounds, we decided to evaluate the activity of several diarylheptanoids derived from curcumin (diferuloyl methane) against the extracellular form (promastigotes) of L. amazonensis. Furthermore, an experiment against the intracellular form of the parasite (amastigotes) was carried out, comparing the most active compound among the curcumin derivatives (the methylcurcumin) with des-O-methylcentrolobine, the most active diarylheptanoid derived from C. sclerophyllum.

Piperine as a phytogenic additive in broiler diets

Abstract – The objective of this work was to determine the effect of piperine as a phytogenic additive in chicken broiler diet. Seven-day-old male chicks were randomly allocated in four experimental treatments (n = 24), with four replicates (n = 6). The piperine was added to diets at concentrations of 0, 60, 120, and 180 -mg kg 1 for 35 consecutive days. The following were evaluated: biochemical, hematological and histopathological parameters; performance and carcass yield. Histomorphometric analyses were also carried out. The addition of 120 and 180 mg kg -1 of piperine did not alter broiler body weight and feed conversion, whereas 60 mg kg -1 of piperine interfered positively in both parameters from 36 to 42 days of age and significantly increased the absorption surface of the duodenum and the ileum. No macroscopic alteration in organ size and color was observed in the broilers fed diets with the evaluated concentrations of piperine. The supplementation of 120 and 180 -mg kg 1 of piperine is toxic to liver tissue and reduces the absorption surface of the jejune. The diet supplemented with 60 -mg kg 1 of piperine is safe.Index terms:

Oral administration of piperine for the control of aflatoxin intoxication in rats.

Aflatoxins are mycotoxins that have important toxic effects on human and animal health, even if consumed at low doses. The oral administration of piperine (1.12 mg/kg) during 23 days in rats seemingly interfered with the toxicity of aflatoxins, decreasing hepatic injuries and the leukocyte depletion in experimentally intoxicated animals.

The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies

Curcumin (CUR) is the major constituent of the rhizomes of Curcuma longa and has been widely investigated for its chemotherapeutic properties. The well-known activity of CUR against Leishmania sp., Trypanosoma brucei and Plasmodium falciparum led us to investigate its activity against Trypanosoma cruzi. In this work, we tested the cytotoxic effects of CUR and other natural curcuminoids on different forms of T. cruzi, as well as the ultrastructural changes induced in epimastigote form of the parasite. CUR was verified as the curcuminoid with more significant trypanocidal properties (IC50 10.13 μM on epimastigotes). Demethoxycurcumin (DMC) was equipotent to CUR (IC50 11.07 μM), but bisdemethoxycurcumin (BDMC) was less active (IC50 45.33 μM) and cyclocurcumin (CC) was inactive. In the experiment with infected murine peritoneal macrophages all diarylheptanoids were more active than the control in the inhibition of the trypomastigotes release. The electron microscopy images showed ultrastructural changes associated with the cytoskeleton of the parasite, indicating tubulin as possible target of CUR in T. cruzi. The results obtained by flow cytometry analysis of DNA content of the parasites treated with natural curcuminoids suggested a mechanism of action on microtubules related to the paclitaxel`s mode of action. To better understand the mechanism of action highlighted by electron microscopy and flow cytometry experiments we performed the molecular docking of natural curcuminoids on tubulin of T. cruzi in a homology model and the results obtained showed that the observed interactions are in accordance with the IC50 values found, since there CUR and DMC perform similar interactions at the binding site on tubulin while BDMC do not realize a hydrogen bond with Lys163 residue due to the absence of methoxyl groups. These results indicate that trypanocidal properties of CUR may be related to the cytoskeletal alterations.

CURCUMINA, O PÓ DOURADO DO AÇAFRÃO-DA-TERRA: INTROSPECÇÕES SOBRE QUÍMICA E ATIVIDADES BIOLÓGICAS

Turmeric, obtained from the dried rhizomes of Curcuma longa (Zingiberaceae), is a golden colored material, commonly used around the world for seasoning and coloring food dishes. Since antiquity, turmeric has been widely used in the treatment of several diseases in traditional Chinese and Indian medicine (Ayurveda), where it is also known by other names such as Kanchani (goddess gold) or also Gauri (having a bright and luminous face), a designation stemming from the gilded appearance of the plant material. Curcumin, the main chemical component of turmeric, is responsible both for its properties as dyes as well as its biological activities. This diarylheptanoid was first isolated almost two centuries ago and had its chemical structure determined in 1910 as being diferuloylmethane. Subsequently, more detailed and relevant data were obtained furthering the understanding of structural features of curcumin. The classical methodology for the synthesis of curcumin and other curcuminoids was described in 1960 by Pabon. Subsequently, different variations on this methodology have been developed, culminating with the synthesis of different curcuminoids. Several studies have been published in recent years on the biological activities exhibited by curcumin including its antioxidant, antitumor, anti-inflammatory, antiviral, antibacterial, antifungal, antimalarial and leishmanicidal activities.Turmeric, obtained from the dried rhizomes of Curcuma longa (Zingiberaceae), is a golden colored material, commonly used around the world for seasoning and coloring food dishes. Since antiquity, turmeric has been widely used in the treatment of several diseases in traditional Chinese and Indian medicine (Ayurveda), where it is also known by other names such as Kanchani (goddess gold) or also Gauri (having a bright and luminous face), a designation stemming from the gilded appearance of the plant material. Curcumin, the main chemical component of turmeric, is responsible both for its properties as dyes as well as its biological activities. This diarylheptanoid was first isolated almost two centuries ago and had its chemical structure determined in 1910 as being diferuloylmethane. Subsequently, more detailed and relevant data were obtained furthering the understanding of structural features of curcumin. The classical methodology for the synthesis of curcumin and other curcuminoids was described in 1960 by Pabon. Subsequently, different variations on this methodology have been developed, culminating with the synthesis of different curcuminoids. Several studies have been published in recent years on the biological activities exhibited by curcumin including its antioxidant, antitumor, anti-inflammatory, antiviral, antibacterial, antifungal, antimalarial and leishmanicidal activities.

Challenges in the chemotherapy of Chagas disease: Looking for possibilities related to the differences and similarities between the parasite and host

Almost 110 years after the first studies by Dr. Carlos Chagas describing an infectious disease that was named for him, Chagas disease remains a neglected illness and a death sentence for infected people in poor countries. This short review highlights the enormous need for new studies aimed at the development of novel and more specific drugs to treat chagasic patients. The primary tool for facing this challenge is deep knowledge about the similarities and differences between the parasite and its human host.

Piperine, its Analogues and Derivatives: Potencial as Antiparasitic Drugs

This paper describes the importance and potentiality of natural piperine as precursor of new bioactive molecules. This natural product has the fruits of black pepper (Piper nigrum, Piperaceae) as its main source. We focused herein its potential antiparasitic activity against two important protozoa of the Trypanosomatidae family: Trypanosoma cruzi, the causative agent of Chagas` disease; and Leishmania sp., which involves a complex of protozoan responsible for leishmaniasis. These two diseases are responsible for different forms of severe clinical manifestations which can culminate in the death of affected patients. In addition, some aspects involving the accessibility of this natural product; extraction methods; as well as its biosynthesis are also discussed herein.

An Alternative Mechanism for the 1,4-Asymmetric Induction in the Stereoselective Addition of (R)-Pantolactone to 2-Phenylpropylketene

An alternative mechanism for the 1,4-assymmetric induction in the stereoselective addition of (R)-pantolactone to 2-phenylpropylketene was theoretically investigated. A mechanism involving an intermolecular proton transfer assisted by two amine molecules was proposed, which considered the active participation of the dimethylethylamine and its ion as proton transfer agents. In the first step, a neutral dimethylethylamine interacts with the seven-membered ring of the enol intermediate. A specific acid-base interaction is established between the hydroxyl group of the enol and the nitrogen atom of the dimethylethylamine. The neutral dimethylethylamine is basic enough to remove the proton. Another protonated dimethylethylamine is considered to donate its proton to the C=C double bond to give the desired products. The stereochemical outcome was defined by the way that the neutral and protonated dimethylethylamine approached to the enol. The diastereoisomeric ratio found is in good agreement with experiments [for (S, R) and (R, R) it is 99:1].

Síntese, caracterização e estudo da atividade inibitória de novas dialquilfosforilarilidrazonas sobre o crescimento de tripanossomatídeos

A new series of dialkylphosphorylhydrazones was synthesized through the condensation of aromatic aldehydes with different phosphorylhydrazines. All synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR and 31P-NMR spectroscopies. The in vitro investigation of the activity of these compounds against Leishmania amazonensis promastigotes and epimastigotes of T. cruzi, showed an efficient inhibition of proliferation, at non toxic concentrations to mammalian cells. The results have shown some derivatives as potential antiparasitic agents against trypanosomatids.

Germinação de sementes de alface e de duas ervas invasoras com a aplicação de um novo análogo do estrigol, sintetizado a partir do safrol

O estrigol e um sesquiterpeno natural que possui elevada atividade como estimulante da germinacao, principalmente de sementes de especies invasoras, pertencentes aos generos Striga e Orobanche. Solucoes contendo 0,01; 0,1; 10 e 1000 mg/L de um novo analogo de estrigol, sintetizado a partir de um alilbenzeno natural, o safrol (isolado do oleo de sassafraz), foram aplicadas em sementes de alface e de Ipomoea grandifolia e Bidens pilosa. Observou-se que houve efeito estimulador na germinacao das sementes das ervas invasoras, sem afetar a germinacao da alface. Os resultados indicam que essa substância apresenta potencial de uso para estimular a germinacao de sementes de ervas invasoras, que poderiam ser eliminadas do solo, antes do plantio de hortalicas como a alface.