Efeitos do ácido naftalenoacético no desenvolvimento in vitro de Cattleya bicolor Lindl. (Orchidaceae)

The techniques of in vitro micropropagation allow the production of large amounts of plants. However, when transferred to the natural environment these plants are susceptible to rapid water loss. The induction of a larger number of roots in orchid plants propagated in vitro would provide a greater water uptake, thus reducing the effects of water loss and increasing the probability of plant survival. The present study aimed to analyze the effects of the synthetic auxin naphthalene-1-acetic acid (NAA) on the in vitro development of plants of Cattleya bicolor, especially regarding root formation. A quantitative analysis of biometric variables of plants grown in different concentrations of NAA (0.0; 0.25; 0.5; 1 and 2 mg.L-1) during 180 and 360 days were carried out. In 360 days, addition of 0.5 mg.L-1 NAA significantly promoted plant growth, increasing length and dry mass of shoot and root portion in relation to the control. Toxicity evidences were detected at 2 mg.L-1 NAA. Therefore, the use of 0.5 mg.L-1 NAA not only promoted the de novo formation and longitudinal growth of roots, but also stimulated shoot development of C. bicolor plants. The results presented in this paper represent an important scientific advance since the growth of most Orchidaceae species is very slow when compared to other herbaceous plant families.O cultivo in vitro permite a produção de grande quantidade de plantas. Entretanto, quando são transferidas para o ambiente natural, estas plantas se tornam susceptíveis ao rápido dessecamento. O aumento do número de raízes de orquídeas propagadas por meio dessa técnica possibilitaria maior absorção de água, reduzindo os efeitos da dessecação e aumentando a probabilidade de sobrevivência das plantas. O presente trabalho analisou os efeitos da auxina ácido naftalenoacético (ANA) sobre o desenvolvimento in vitro de plantas de Cattleya bicolor, especialmente com relação à formação de raízes. Para tanto, foi realizada a análise quantitativa de parâmetros biométricos de plantas incubadas em diferentes concentrações de ANA (0,0; 0,25; 0,5; 1 e 2 mg.L-1) durante 180 e 360 dias. Em 360 dias, a adição de 0,5 mg.L-1 de ANA promoveu significativamente o crescimento, aumentando o comprimento e a massa seca caulinar e radicial em relação ao controle. A concentração de 2mg L-1 apresentou indícios de toxicidade. Portanto, a utilização de 0,5 mg.L-1 de ANA promoveu a neoformação e o crescimento longitudinal das raízes, além de estimular o desenvolvimento caulinar em plantas de C. bicolor. Os resultados descritos neste trabalho representam um importante avanço científico, uma vez que o crescimento é bastante lento na maioria das espécies da família Orchidaceae, comparativamente às outras famílias de plantas herbáceas

Synthetic indole and melatonin derivatives exhibit antimalarial activity on the cell cycle of the human malaria parasite Plasmodium falciparum

Discovering the mechanisms by which cell signaling controls the cell cycle of the human malaria parasite Plasmodium falciparum is fundamental to designing more effective antimalarials. To better understand the impacts of melatonin structure and function on the cell cycle of P. falciparum, we have synthesized two families of structurally-related melatonin compounds (7–11 and 12–16). All synthesized melatonin analogs were assayed in P. falciparum culture and their antimalarial activities were measured by flow cytometry. We have found that the chemical modification of the carboxamide group attached at C-3 position of the indole ring of melatonin (6) was crucial for the action of the indole-related compounds on the P. falciparum cell cycle. Among the melatonin derivatives, only the compounds 12, 13 and 14 were capable of inhibiting the P. falciparum growth in low micromolar IC50. These results open good perspectives for the development of new drugs with novel mechanisms of action

Synthesis and Antiplasmodial Activity of Betulinic Acid and Ursolic Acid Analogues

More than 40% of the World population is at risk of contracting malaria, which affects primarily poor populations in tropical and subtropical areas. Antimalarial pharmacotherapy has utilised plant-derived products such as quinine and artemisinin as well as their derivatives. However, worldwide use of these antimalarials has caused the spread of resistant parasites, resulting in increased malaria morbidity and mortality. Considering that the literature has demonstrated the antimalarial potential of triterpenes, specially betulinic acid (1) and ursolic acid (2), this study investigated the antimalarial activity against P. falciparum chloroquine-sensitive 3D7 strain of some new derivatives of 1 and 2 with modifications at C-3 and C-28. The antiplasmodial study employed flow cytometry and spectrofluorimetric analyses using YOYO-1, dihydroethidium and Fluo4/AM for staining. Among the six analogues obtained, compounds 1c and 2c showed excellent activity (IC50 = 220 and 175 nM, respectively) while 1a and b demonstrated good activity ( IC50 = 4 and 5 mu M, respectively). After cytotoxicity evaluation against HEK293T cells, 1a was not toxic, while 1c and 2c showed IC50 of 4 mu M and a selectivity index (SI) value of 18 and 23, respectively. Moreover, compound 2c, which presents the best antiplasmodial activity, is involved in the calcium-regulated pathway(s).Instituto Nacional de Ciencia e Tecnologia para Inovacao Farmaceutica (INCTif, Brazil)Instituto Nacional de Ciencia e Tecnologia para Inovacao Farmaceutica (INCT-if, Brazil)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), BrazilConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq-Brazil)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), BrazilCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES-Brazil)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), BrazilFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil)Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil)Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil)FAPESPFAPES

Two series of new semisynthetic triterpene derivatives: differences in anti-malarial activity, cytotoxicity and mechanism of action

Background\ud The discovery and development of anti-malarial compounds of plant origin and semisynthetic derivatives thereof, such as quinine (QN) and chloroquine (CQ), has highlighted the importance of these compounds in the treatment of malaria. Ursolic acid analogues bearing an acetyl group at C-3 have demonstrated significant anti-malarial activity. With this in mind, two new series of betulinic acid (BA) and ursolic acid (UA) derivatives with ester groups at C-3 were synthesized in an attempt to improve anti-malarial activity, reduce cytotoxicity, and search for new targets. In vitro activity against CQ-sensitive Plasmodium falciparum 3D7 and an evaluation of cytotoxicity in a mammalian cell line (HEK293T) are reported. Furthermore, two possible mechanisms of action of anti-malarial compounds have been evaluated: effects on mitochondrial membrane potential (ΔΨm) and inhibition of β-haematin formation.\ud \ud Results\ud Among the 18 derivatives synthesized, those having shorter side chains were most effective against CQ-sensitive P. falciparum 3D7, and were non-cytotoxic. These derivatives were three to five times more active than BA and UA. A DiOC6(3) ΔΨm assay showed that mitochondria are not involved in their mechanism of action. Inhibition of β-haematin formation by the active derivatives was weaker than with CQ. Compounds of the BA series were generally more active against P. falciparum 3D7 than those of the UA series.\ud \ud Conclusions\ud Three new anti-malarial prototypes were obtained from natural sources through an easy and relatively inexpensive synthesis. They represent an alternative for new lead compounds for anti-malarial chemotherapy.This work was supported by grants and financial support from Brazilian Agencies CAPES, CNPq, INCT-IF, Malaria-PRONEX, INCT-INBEQMeDI, FAPESP and the Graduate Programme in Pharmaceutical Sciences (PPGCF/UFRGS). The authors are also grateful to the apple samples from Tecnovin do Brasil LTDA, RS, Brazil. We thank Prof Dr N P Lopes (USP-RP) for HRMS analysis. LNC and MSM received FAPESP Fellowships

Estudo da germinação e crescimento in vitro de Hadrolaelia tenebrosa (Rolfe) Chiron & V.P. Castro (Orchidaceae), uma espécie da flora brasileira ameaçada de extinção

As orquídeas são espécies seriamente ameaçadas de extinção. Por isso, estudos sobre a propagação e desenvolvimento dessas plantas são extremamente importantes. Assim, este trabalho procurou estudar a influência do meio de cultura na germinação in vitro de sementes de Hadrolaelia tenebrosa, no desenvolvimento inicial dos protocormos até a formação das plântulas, bem como no crescimento dessas durante o primeiro ano de cultivo in vitro. Os resultados demonstraram que o método ideal para a multiplicação de Hadrolaelia tenebrosa é a utilização do meio Knudson C para a germinação das sementes. Após seis meses as plântulas devem ser transferidas para o meio VW e nele mantidas até o início da aclimatização. Ressalta-se o fato de que para essa espécie o meio de cultura mais eficaz para a germinação, não foi o mais adequado para o desenvolvimento das plantas. Estas informações são de grande importância para a otimização do processo de propagação de espécies de orquídeas

The role of melatonin in parasite biology

Regarded as the circadian hormone in mammals, melatonin is a highly conserved molecule, present in nearly all species. in this review, we discuss the role of this indolamine and its precursors in the cell biology of parasites and the role of the molecule in the physiology of the host. in Plasmodium, melatonin can modulate intracellular concentrations of calcium and CAMP, which in turn can regulate kinase activity and cell cycle. in Trypanosoma infections, modulation of the immune system by melatonin is extremely important in controlling the parasite population. Melatonin also contributes to the inflammatory response to Toxoplasma gondii infection. Thus, there are a number of unique adaptations involving intricate connections between melatonin and the biology of the parasite-host relationship. (C) 2011 Elsevier B.V. All rights reserved.Universidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilUniv São Paulo, Inst Biociencias, Dept Fisiol, São Paulo, BrazilUMDNJ, New Jersey Med Sch, Dept Physiol & Pharmacol, Newark, NJ USAUniv Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USAUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilWeb of Scienc

Efeitos do ácido naftalenoacético no desenvolvimento in vitro de Cattleya bicolor Lindl. (Orchidaceae)

The techniques of in vitro micropropagation allow the production of large amounts of plants. However, when transferred to the natural environment these plants are susceptible to rapid water loss. The induction of a larger number of roots in orchid plants propagated in vitro would provide a greater water uptake, thus reducing the effects of water loss and increasing the probability of plant survival. The present study aimed to analyze the effects of the synthetic auxin naphthalene-1-acetic acid (NAA) on the in vitro development of plants of Cattleya bicolor, especially regarding root formation. A quantitative analysis of biometric variables of plants grown in different concentrations of NAA (0.0; 0.25; 0.5; 1 and 2 mg.L-1) during 180 and 360 days were carried out. In 360 days, addition of 0.5 mg.L-1 NAA significantly promoted plant growth, increasing length and dry mass of shoot and root portion in relation to the control. Toxicity evidences were detected at 2 mg.L-1 NAA. Therefore, the use of 0.5 mg.L-1 NAA not only promoted the de novo formation and longitudinal growth of roots, but also stimulated shoot development of C. bicolor plants. The results presented in this paper represent an important scientific advance since the growth of most Orchidaceae species is very slow when compared to other herbaceous plant families.O cultivo in vitro permite a produção de grande quantidade de plantas. Entretanto, quando são transferidas para o ambiente natural, estas plantas se tornam susceptíveis ao rápido dessecamento. O aumento do número de raízes de orquídeas propagadas por meio dessa técnica possibilitaria maior absorção de água, reduzindo os efeitos da dessecação e aumentando a probabilidade de sobrevivência das plantas. O presente trabalho analisou os efeitos da auxina ácido naftalenoacético (ANA) sobre o desenvolvimento in vitro de plantas de Cattleya bicolor, especialmente com relação à formação de raízes. Para tanto, foi realizada a análise quantitativa de parâmetros biométricos de plantas incubadas em diferentes concentrações de ANA (0,0; 0,25; 0,5; 1 e 2 mg.L-1) durante 180 e 360 dias. Em 360 dias, a adição de 0,5 mg.L-1 de ANA promoveu significativamente o crescimento, aumentando o comprimento e a massa seca caulinar e radicial em relação ao controle. A concentração de 2mg L-1 apresentou indícios de toxicidade. Portanto, a utilização de 0,5 mg.L-1 de ANA promoveu a neoformação e o crescimento longitudinal das raízes, além de estimular o desenvolvimento caulinar em plantas de C. bicolor. Os resultados descritos neste trabalho representam um importante avanço científico, uma vez que o crescimento é bastante lento na maioria das espécies da família Orchidaceae, comparativamente às outras famílias de plantas herbáceas