Marine drugs for cancer: surfacing biotechnological innovations from the oceans

This review will discuss the contributions of marine natural molecules, a source only recently found to have pharmaceutical prospects, to the development of anticancer drugs. Of the seven clinically utilized compounds with a marine origin, four are used for the treatment of cancer. The development of these drugs has afforded valuable knowledge and crucial insights to meet the most common challenges in this endeavor, such as toxicity and supply. In this context, the development of these compounds will be discussed herein to illustrate, with successful examples provided by cytarabine, trabectedin, eribulin and brentuximab vedotin, the steps involved in this process as well as the scientific advances and technological innovation potential associated with developing a new drug from marine resources.

Influence of magnification and superimposition of structures on cephalometric diagnosis

OBJECTIVE: The purpose of this study was to assess the influence of magnification and superimposition of structures on CBCT-generated lateral cephalometric radiographs (LCR) using different segments of the cranium. METHODS: CBCT scans of 10 patients were selected. Four LCR were generated using Dolphin Imaging(r) software: full-face, right side, left side and center of the head. A total of 40 images were imported into Radiocef Studio 2(r), and the angles of the most common cephalometric analyses were traced by the same observer twice and within a 10-day interval. Statistical analyses included intraexaminer agreement and comparison between methods by means of intraclass correlation coefficient (ICC) and Bland-Altman agreement tests. RESULTS: Intraexaminer agreement of the angles assessed by ICC was excellent (> 0.90) for 83% of measurements, good (between 0.75 and 0.90) for 15%, and moderate (between 0.50 and 0.75) for 2% of measurements. The comparison between methods by ICC was excellent for 68% of measurements, good for 26%, and moderate for 6%. Variables presenting wider confidence intervals (> 6o) in the Bland-Altman tests, in intraexaminer assessment, were: mandibular incisor angle, maxillary incisor angle, and occlusal plane angle. And in comparison methods the variables with wider confidence interval were: mandibular incisor, maxillary incisor, GoGn, occlusal plane angle, Frankfort horizontal plane (FHP), and CoA. CONCLUSION: Superimposition of structures seemed to influence the results more than magnification, and neither one of them significantly influenced the measurements. Considerable individual variability may occur, especially for mandibular and maxillary incisors, FHP and occlusal plane. .

OBJETIVO: o objetivo do presente estudo foi avaliar a influência da sobreposição estrutural e da magnificação nas radiografias cefalométricas laterais (RCL) geradas por meio de tomografias computadorizadas de feixe cônico (TCFC), usando diferentes segmentos do crânio. MÉTODOS: foram selecionadas 10 tomografias de pacientes. Quatro RCL foram geradas usando Dolphin Imaging, sendo face total, lado direito, lado esquerdo e o centro da cabeça. Um total de 40 imagens foi importado para o Radiocef Studio, e os ângulos das análises cefalométricas mais comuns foram medidos pelo mesmo observador, duas vezes, em um intervalo de 10 dias. As análises estatísticas incluíram concordância intraexaminador e comparação entre os métodos por meio do coeficiente de correlação intraclasse (ICC) e testes de concordância de Bland-Altman. RESULTADOS: a concordância intraexaminador dos ângulos avaliados pelo ICC foi excelente (> 0,90) para 83% das medições, boa (entre 0,75 e 0,90) para 15%, e moderada (entre 0,50 e 0,75) para 2% das medições. A comparação entre os métodos por ICC foi excelente para 68% das medições, boa para 26% e moderada para 6%. As variáveis que apresentaram intervalos de confiança mais amplos (> 6°) nos testes de Bland-Altman, na avaliação intraexaminador, foram: incisivo superior, incisivo inferior e plano oclusal, enquanto nos métodos de comparação, as variáveis com intervalos de confiança mais amplos foram: incisivo inferior, incisivo superior, GoGn, ângulo do plano oclusal, plano horizontal de Frankfort e CoA. CONCLUSÃO: a sobreposição estrutural pareceu influenciar os resultados mais do que a magnificação, mas os métodos não influenciaram significativamente as medições. Considerável variabilidade individual pode ocorrer especialmente para os incisivos superiores e inferiores, plano horizontal de Frankfort e plano oclusal. .

Introduction of soft drinks and processed juice in the diet of infants attending public day care centers / Introdução de refrigerantes e sucos industrializados na dieta de lactentes que frequentam creches públicas

OBJECTIVE: Identifying at what age infants enrolled in public day care centers are introduced to soft drinks and industrialized juice, as well as comparing the nutritional composition of these goods with natural fruit juice. METHODS: A cross-sectional study with the mothers of 636 children (aged 0 to 36 months) from nurseries of day care centers, who were asked questions about the age of feeding introduction. This study evaluated the proximate composition of soft drinks and artificial juice, comparing them with those of natural fruit juice regarding energy, sugar, fiber, vitamin C, and sodium values. The chemical composition of fruit juice was obtained by consulting the Table of Food Composition and, for industrialized drinks, the average nutritional information on the labels of the five most consumed product brands. RESULTS: The artificial drinks were consumed before the first year of life by more than half of the children studied, however, approximately 10% consumed them before the age of 6 months. With regard to the comparison among the drinks, artificial fruit juice beverages and soft drinks proved to contain from nine to 13 times higher amounts of sodium, and 15 times less vitamin C than natural juices. CONCLUSIONS: The introduction of soft drinks and industrialized juice in the diet of infants was inopportune and premature.. When compared to natural fruit juice, these have inferior nutritional composition, which suggests the urgent need for measures based on strategies for food and nutrition education in order to promote awareness and the maintenance of healthy eating habits. .

OBJETIVO: Identificar a idade de introdução do refrigerante e de sucos industrializados na dieta de lactentes matriculados em berçários de creches públicas e comparar as composições nutricionais dessas bebidas com as do suco de fruta natural. MÉTODOS: Estudo transversal com 636 crianças (de zero a 36 meses) de berçários de creches, cujas mães foram entrevistadas sobre idade de introdução dos alimentos. Avaliaram-se as composições centesimais do refrigerante e sucos industrializados, comparando-as com as do suco de laranja natural para valor energético, açúcar, fibra, vitamina C e sódio. A composição centesimal do suco de laranja foi obtida por meio de consulta à Tabela de Composição de Alimentos e, para as bebidas industrializadas, utilizaram-se as médias das informações nutricionais contidas nos rótulos de cinco marcas mais consumidas dos produtos. RESULTADOS: O refrigerante e suco industrializado foram consumidos antes do primeiro ano de vida por mais da metade das crianças estudadas, sendo que cerca de 10% o consumiram antes dos seis meses. Quando comparadas à composição do suco de laranja natural, bebidas forneceram quantidades de 9 a 13 vezes superiores de sódio e 15 vezes inferiores de vitamina C. CONCLUSÕES: A introdução de refrigerantes e sucos industrializados na dieta dos lactentes foi inoportuna e precoce. Comparados ao suco de fruta natural, tais bebidas possuem composição nutricional inferior, sugerindo a necessidade de medidas fundamentadas em estratégias de educação alimentar e nutricional como forma de promover a formação e manutenção de hábitos alimentares saudáveis. .

In vitro anti-proliferation/cytotoxic activity of epingaione and its derivatives on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells / Actividad citotóxica antiproliferativa in vitro de la epingaiona y sus derivados, sobre el neuroblastoma humano sh-sy5y y las células del sarcoma te-671

Epingaione (4-Methyl-1-(5-methyl-2, 3,4,5-tetrahydro-[2,3']bifuranyl-5-yl)-pentan-2-one) was isolated as one of the major lipophilic secondary metabolites from the leaves and stems of Bontia daphnoides L. The compound gave 79.24and 50.83anti-proliferation/cytotoxic activity on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells in vitro at 50 pg/mL, respectively. Epingaione was transformed into eleven derivatives under laboratory conditions using ethanol, some gave greater anti-proliferation/cytotoxic activity on the cancer cell lines tested. One of the derivatives (compound 2) with enhanced cytotoxic activity was elucidated as 5'-Ethoxy-5-methyl-5-(4-methyl-2-oxo-pentyl)-2,3,4,5-tetrahydro-5'H-[2,3']bifuranyl-2'-one. Both epingaione and compound 2 caused an accumulation of arrested or dead SH-SY5Y neuroblastoma in the m-phase of the cell cycle as revealed by the m-phase specific marker KE 67.

La epingaiona (4-Metil-1-(5-metil-2,3,4,5-tetrahidro-[2,3']bifuranil-5-il)-pentan-2-uno) fue aislada como uno de los principales metabolitos lipofilicos secundarios de las hojas y tallos de Bontia daphnoides L. El compuesto produjo 79.24 % y 50.83 % de actividad citotóxica/anti-proliferación sobre el neuroblastoma humano SH-SY5Y y las células del sarcoma TE-671 in vitro a 50 µg/mL, respectivamente. La epingaiona fue transformada en once derivados en condiciones de laboratorio, utilizando etanol. Algunos produjeron mayor actividad citotóxica y antiproliferativa sobre las líneas celulares cancerosas sometidas a ensayo. Uno de los derivados (compuesto 2) de elevada actividad citotóxica fue identificado como 5'-Etoxi-5-metil-5-(4-metil-2-oxo-pentil)-2,3,4,5-tetrahidro-5'H- [2,3']bifuranil-2'-uno. Tanto la epingaiona como el compuesto 22 causaron una acumulación de neuroblastomas SH-SY5Y muertos o detenidos en la fase m del ciclo celular, según lo revela el marcador KE 67 específico de la fase m.

Arylfurans as potential Trypanosoma cruzi trypanothione reductase inhibitors

The natural lignans veraguensin and grandisin have been reported to be active against Trypanosoma cruzi bloodstream forms. Aiming at the total synthesis of these and related compounds, we prepared three 2-arylfurans and eight 2,5-diarylfurans. They were evaluated for their potential as T. cruzi trypanothione reductase (TR) inhibitors as well against the parasite's intracellular (amastigote) and bloodstream (trypomastigote) forms. Compound 12 was the most effective against TR with an IC50 of 48.5 æM while 7 and 14 were active against amastigotes, inhibiting the parasite development by 60 percent at 20 æg/ml (59 and 90 æM, respectively). On the other hand, none of the compounds was significantly active against the parasite bloodstream forms even at 250 æg/ml (0.6-1.5 mM).

In vitro antiviral activity of bael (Aegle marmelos Corr) upon human coxsackieviruses B1-B6.

The in-vitro antiviral activity of a series of compounds in samples extracted from various parts of the Indian holy tree, Bael (Aegle marmelos corr.) were evaluated for their efficacy against human coxsackieviruses B1-B6. The inhibitory concentrations (IC50) for leaves (L1 and L2) stem and stem bark (S1, S2, S3 and S4) fruit (F1 and F2micro) root and root bark (R1 and R2) and pure compound, the marmelide were 1000 microg/ml (for L1 and L2), 1000 microg/ml (for S1, S2, S3 and S4), 1000 microg/ml (for F1) and 500 microg/ml (for F2) 250 microg/ml (for R1) and 500 microg/ml (for R2) and 62.5 microg/ml for marmelide respectively by plaque inhibition assay at 96 hrs. On the other hand, the corresponding value for Ribavirin, a standard antiviral drug, was 2000 microg/ml for the same viruses at the same time period. These concentrations did not exhibit any toxicity to Vero cells, the host subtoxic concentrations were 5000 microg/ml for leaf and stem fractions 2000 microg/ml for fruit fractions 500 and 1000 microg/ml for root fractions 250 microg/ml for marmelide and 2000 microg/ml for Ribavirin. The cytotoxic concentrations were 8000 microg/ml for leaf and stem compounds 4000 mg/ml for fruit; 1000 microg/ml and 2000 microg/ml for root 500 microg/ml for marmelide and 4000 microg/ml for ribavirin at 96 hrs. These were also confirmed by trypan blue dye exclusion test and further passaging of cells. Additionally pretreatment of host cells, virus inactivation, yield reduction and effect of time of addition assays against coxsackievirus B3 suggested that marmelide was most effective as a virucidal agent besides interfering at early events of its replicative cycle like adsorption, penetration, at various steps in single cycle growth curve and effect of time of addition.

Heterocyclic synthesis with nitriles: synthesis of some novel furo [2,3-b] nicotinic acid derivatives of anticipated biological activity

2-Amino-5-phenylfuran-3-carbonitrile 2 reacts with malonic acid derivatives 3a-d and 6 to afford the furo [2, 3-b] pyridine derivatives 5a-c. Compounds 2 reacts with urea and thiourea to afford the pyrrole derivative 10 which was also obtained from 2 and ammonium acetate. The reaction of 2 with the arylidene derivatives 11a-f yield the furo [2, 3-b] nicotinonitrile derivatives 13a, c, e; which were hydrolyzed to the nicotinic acid derivatives 14a, c, e, respectively. Compound 2 reacts also with the acrylic acid derivatively 15a-c to afford the furo [2, 3-b] nicotinic acid derivatives 17a-c, which were hydrolyzed to give the furo [2, 3-b] nicotinic acid 18. Compounds 5b, c undergo S-or N-alkylation on reaction with phenacyl bromide 19a and ethyl bromoacetate 19b to yield compounds 20a-d, respectively. Compound 5b reacts with hydrazine hydrate to afford the hydrazino derivative 22 which could be cyclized into the furopyridopyrazole derivative 23. Compound 5b reacts also with I2/Kl in DMF to afford the disulphide 24

Biogenetic relationship of the furanoacetylene phytoalexins in viciafaba

The biogenetic relationship between wyerone, wyerol and the 11, 12-dihydro analogues has been investigated. Labeled wyerone and dihydrowyerone were obtained by feeding sodium [2-14C] acetate to CuCl2-induced V. faba cotyledons, and separation by HPLC. Some of the wyerone was used for semisynthesis of wyerol. The three title compounds were then fed to induced bean cotyledons to establish any possible interconversion. Incorporation data indicated a 0.45% conversion of wyerone into dihydrowyerone and 3% reversed conversion. The highest incorporation was 13.3% conversion of wyerol into wyerone, accompanied by a small conversion [0.15%] of wyerol into dihydrowyerone. The results indicated that wyerone has been derived from wyerol, most probably, by oxidation

Synthesis and characterization of new cobalt [II] and copper [II] complexes of tetrazamacrocyclic ligands

A new macrocyclic Co[II] complex was prepared by metal-controlled condensation reaction between furan-2,3-dicarbaldehyde and 1,2-diaminoethane. Simple reactions led to the isolation of isothiocyanate and nitrite derivatives. Template synthesis of the macrocyclic Cu[II] complex was unsuccessful, however reaction of furan-2,3-dicarbaldehyde and 1,3-diaminopropane in ethanol gives a tetraazamacrocyclic ligand [L], Cu[II] complexes of L were prepared by a simple addition reaction. Various physical properties of the complexes have been studied