Showing papers by "Angelo C. Pinto published in 2011"

Novel 1,2,3-triazole derivatives for use against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain.

Abstract: The purpose of this study was to prepare various 4-substituted N-phenyl-1,2,3-triazole derivatives using click chemistry. The derivatives were screened in vitro for antimicrobial activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294) using the Alamar Blue susceptibility test. The activity was expressed as the minimum inhibitory concentration (MIC) in μg/mL (μM). Derivatives of isoniazid (INH), (E)-N'-[(1-aryl)-1H-1,2,3-triazole-4-yl)methylene] isonicotinoyl hydrazides, exhibited significant activity with MIC values ranging from 2.5 to 0.62 μg/mL. In addition, they displayed low cytotoxicity against liver cells (hepatoma HepG2) and kidney cells (BGM), thereby providing a high therapeutic index. The results demonstrated the potential and importance of developing new INH derivatives to treat mycobacterial infections.

Docking of the alkaloid geissospermine into acetylcholinesterase: a natural scaffold targeting the treatment of Alzheimer’s disease

Abstract: Pharmacological studies from our group [Lima et al. Pharmacol Biochem Behav 92:508, (2009)] revealed that geissospermine (GSP), the major alkaloid of the bark extract of Brazilian Geissospermum vellosii, inhibits acetylcholinesterases (AChEs) in the brains of rats and electric eels (Electrophorus electricus). However, the binding mode (i.e., conformation and orientation) of this indole-indoline alkaloid into the AChE active site is unknown. Therefore, in order to propose a plausible binding mode between GSP and AChE, which might explain the observed experimental inhibitory activity, we performed comparative automatic molecular docking simulations using the AutoDock and Molegro Virtual Docker (MVD) programs. A sample of ten crystal structures of the Pacific electric ray (Torpedo californica) TcAChE, in complex with ten diverse active site ligands, was selected as a robust re-docking validation test, and also for GSP docking. The MVD results indicate a preferential binding mode between GSP and AChE, in which GSP functional groups may perform specific interactions with residues in the enzyme active site, according to the ligand–protein contacts detected by the LPC/CSU server. Four hydrogen bonds were detected between GSP and Tyr121, Ser122, Ser200, and His440, in which the last two residues belong to the catalytic triad (Ser200···His440···Glu327). Hydrophobic and π–π stacking interactions were also detected between GSP and Phe330 and Trp84, respectively; these are involved in substrate stabilization at the active site. This study provides the basis to propose structural changes to the GSP structure, such as molecular simplification and isosteric replacement, in order to aid the design of new potential AChE inhibitors that are relevant to the treatment of Alzheimer’s disease.

The mechanism of Sandmeyer's cyclization reaction by electrospray ionization mass spectrometry.

Abstract: Using electrospray ionization (tandem) mass spectrometry (ESI-MS(/MS)) spectrometric experiments, the Sandmeyer reaction was monitored on-line, and key intermediates were intercepted and characterized for the first time. The mechanistic information provided by on-line ESI-MS(/MS) is in accordance with Sandmeyer's proposal, and was made possible by coupling a microreactor on-line to the ESI ion source, which allowed reactions to be screened from 0.7–2.0 s, identifying and characterizing all intermediates that were formed and consumed during the reaction. Copyright © 2011 John Wiley & Sons, Ltd.

Semi-preparative separation of α and β-amyrin by high performance liquid chromatographic

Abstract: The resin obtained from species of the genus Protium (Burseraceae) is formed mostly of pentacyclic triterpenes: α-amyrin and β-amyrin. The separation and purification of these triterpenes were optimized in three steps.

Chlorination of isatins with trichloroisocyanuric acid

Abstract: Isatin and its derivatives have been extensively reported in the literature as having range of potential pharmacological compounds. The Sandmeyer method is the most widely used for isatin synthesis and furnishes different substituted isatins, usually with high yields. Although efficient, the Sandmeyer route has certain limitations, such as the formation of a mixture of regiosiomers and low yields depending on the type and position of the substituent. Thus, overcome these limitations, it is preferable that some derivative isatins be obtained by alternative methods. This article has investigated the chlorination of isatin derivatives using trichloroisocyanuric acid [1,3,5-trichloro1,3,5-triazine-2,4,6-(1H,3H,5H)-trione or TCCA] at different reaction conditions.

Synthesis of new 2-aminocarbohydrate-1,4-naphthoquinone derivatives promoted by ultrasonic irradiation

Abstract: Neste trabalho nos descrevemos o uso do ultrassom na sintese de novas naftoquinonas, 6a-f e 7a-c, contendo na posicao 2 do anel quinonoidico substituintes do tipo aminocarboidratos. Estas substâncias foram preparadas, em condicoes brandas, atraves da reacao da 1,4-naftoquinona (8a) ou do metoxi-lapachol (8b) com diferentes aminocarboidratos 9a-d. As estruturas das substâncias foram confirmadas atraves das tecnicas de RMN de 1H e de 13C-APT, uni- e bi-dimensionais (COSY-1H vs. 1H e HETCOR 1JCH), e por espectrometria de massas de alta resolucao com ionizacao por electrospray (ESI MS).

Anthraquinones from the bark of Senna macranthera

Abstract: acetyl physcion (2-acetyl-1,8-dihydroxy-6-methoxy-3-methyl-9,10-anthraquinone, 2), a rare anthraquinone, was iso- lated from Senna macranthera var. nervosa (Vogel) H.S. Irwin & Barneby (Fabaceae). The chemical structure was elucidated and all 1 H and 13 C NMR chemical shifts were assigned by NMR one- ( 1 HNMR, { 1 H}- 13 CNMR, and APT- 13 CNMR) and two (COSY, NOESY, HMQC and HMBC) dimensional of this natural compound. Furthermore, the minor anthraquinones chrysophanol (3), chrysophanol-8-methyl ether (4) and physcion (5) were characterized by GC-MS analysis. The occurrence of the anthraquinones 3-5 confirms that S. macranthera is a typical representative of the genus Senna.

Synthesis and anti‐Trypanosoma cruzi Activity of β‐Lapachone Analogues.

Abstract: The naphthoquinone analogues of β-lapachone are obtained from methylene and aryl o-quinone methides, generated in situ by Knoevenagel condensation of lawsone (I) with paraformaldehyde (II) or aryl aldehydes (IX), followed by hetero Diels—Alder reaction with different dienophiles.

Fatty acids as chemotaxonomic markers of marine macrophytes from Rio de Janeiro state, Brazil.

Abstract: The distribution of fatty acids in 13 species of macroalgae (Chlorophyta, Ochrophyta and Rhodophyta) and 1 seagrass (Spartina sp), collected on the Rio de Janeiro state coast was determined The results were evaluated in search of correlations between the taxonomic and phylogenetic position of these macrophytes Statistical analyses showed the effectiveness as taxonomic and phylogenetic markers of the distribution of the methyl fatty acid esters in these macrophytes

Uma breve história da química Brasileira

Abstract: a melhor e, ainda, a mais completa descricao da historia da quimica no Brasil e o capitulo escrito por Heinrich Rheinboldt para o livro As ciencias no Brasil, organizado por Fernando de Azevedo (1). Esta historia ganha um novo impulso com o livro A industria quimica e o desenvolvimento do Brasil 1500‐1889, publicado em 1996, por Ernesto Carrara Ju‐ nior e Helio Meirelles, o qual completa uma lacuna que faltava na historia da quimica brasileira (2). Este texto deve ser visto como um ensaio, por nao ter a profundi‐ dade de um artigo academico, como merece a historia da quimica no Brasil. Resume um conjunto de fatos e de marcos historicos, numa otica muito pessoal dos autores, que enxer‐ gam a quimica num contexto mais amplo, nao se limitando apenas a ciencia e a industria quimica. Nao e a visao de um historiador profissional que se dedica a entender as origens da quimica. Os autores pertencem a corrente daqueles que acreditam que a quimica nasce com a elaboracao e transmissao de conhecimentos praticos, cujas origens remontam ao dominio do fogo, a confeccao de artefatos de cerâmica e aos primeiros processos de tinturaria e de fermentacao. Por este ângulo, pode‐se afirmar que a primeira descricao da quimica no Brasil foi feita por Pero Vaz de Caminha na carta que enviou ao rei Dom Manuel para dar noticia da nova terra encontrada. Na carta, con‐ siderada por muitos como a “certidao de nascimento do Brasil”, o escrivao da frota de Pedro Alvares Cabral revela todo o seu espanto com as cores vivas ornamentais dos seus habitantes. Impressionou‐o o vermelho e a tinta negro‐azulada com as quais os indigenas esta‐ vam pintados. Isso da uma amostra do dominio dos processos de extracao de corantes naturais e do tingimento corporal que tinham os habitantes do Novo Mundo. Eles sabiam como extrair o corante vermelho do urucum, a Bixa orellana, e a seiva dos frutos da arvore Genipa americana, de nome genipapo, que ao reagir com a pele, pro‐ duz uma coloracao negro‐azulada (3) e com os quais e produzido um licor muito apreciado, ate os dias de hoje, em todo o Brasil. Da descoberta da nova terra ate o seculo XIX, pode‐se afirmar que os unicos fatos relacionados a ciencia foram protagonizados pelos cronistas que se ocuparam da descricao das virtudes das plantas medicinais da flora nativa, e de elogiarem os ares saudaveis e o clima da Terra de Santa Cruz, depois chamada de Brasil. Algumas plantas medicinais brasileiras dos indigenas, descritas pelos cronistas, enriqueceram as farmacopeias europeias. O seculo XIX foi marcado pela presenca de grandes expedicoes e cientistas estrangeiros que vieram para coletar amostras dos tres reinos da natureza, para enriquecer as colecoes dos museus europeus. O marasmo cientifico de Portugal imposto pela forca da igreja, liderada, principalmente, pela ordem dos jesuitas, que fizeram da censura o instrumento de controle das publicacoes cientificas na metropole e, em consequencia, em todas as suas colonias ultrama‐ rinas, perdurou ate a reforma feita por Sebastiao Jose de Carvalho e Melo (1699‐1782), Conde de Oeiras e, depois Marques de Pombal, o primeiro‐ministro de D. Jose I. Um dos principais baluartes dos jesuitas, a Universidade de Evora, foi extinta em 1759, e a Reforma Pombalina, de 1772, levou a criacao, na Universidade de Coimbra, das Faculdades de Matematica e de Filosofia Natural (ciencias), e a reforma dos estudos de medicina. Novos estabelecimentos cien‐ tificos se fizeram necessarios, originando a construcao de novos edificios destinados ao Laboratorio Quimico, ao Observatorio Astronomico, a Imprensa da Universidade e a instalacao do nucleo inicial do Jardim Botânico (4). Antes da Reforma Pombalina, no Brasil, assim como em Portugal, a ciencia nao “existia”, diferentemente do que acontecia em outros paises da Europa. As unicas discussoes cientificas ocorriam em algumas poucas academias e sociedades cienti‐ ficas, todas de vida muito efemera. No Rio de Janeiro, por exemplo, foi criada, em 1786, a Sociedade Literaria do Rio de Janeiro, que fun‐ cionou regularmente ate 1790, e que se ocupou da discussao de temas cientificos, como o meto‐ do para extracao da tinta do urucum e a analise de aguas, para citar apenas dois assuntos relacio‐ nados diretamente com a quimica, discutidos pelos socios academicos (5). Apesar de a producao de acucar de cana nos engenhos brasileiros ter comecado na Bahia apos 1550, se estendendo depois para os estados de Alagoas e Pernambuco, e a industria extrativista da mineracao ter se iniciado a partir do seculo XVIII, atividades relacionadas a quimica eram praticamente inexistentes.