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Toads of the Rhinella genus have a pair of paratoid glands that store biological secretions of high toxicity and varied chemical composition, rich in biologically active compounds. The present work aimed to carry out the investigation of the metabolomic profile and evaluation of the biological potential of the secretion paratoid glands (PGS) from Rhinella granulosa. The paratoid secretion was collected in the Piauí state (Brazil), extracted with methanol and the extract was analyzed by ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Fifty chemical constituents were identified. The extract showed cytotoxicity against tumor cell lines of the central nervous system (half maximal inhibitory concentration (IC50) = 1.9 µg mL-1) and prostate (IC50 = 1.6 µg mL-1), unsatisfactory antimicrobial potential (minimal inhibitory concentration (MIC) > 312 µg mL-1) and inhibited the enzyme acetylcholinesterase (IC50 = 5.119 mg mL-1). The results presented relevant information about the PGS and contributed to the understanding of the metabolomic and biological potential of R. granulosa.

The main goal was the development of a polysaccharide microcapsule for anticancer application based on guar gum and sodium alginate for the controlled release of hesperidin and betulinic acid by spray drying technique. The microcapsule showed an Encapsulation Efficiency of 98.15 ± 0.34 % for hesperidin and 99.76 ± 0.22 % for betulinic acid. In the release study, the Korsmeyer-Peppas mathematical model was identified as the most adequate to explain the observed release mechanism. In vivo tests were performed in zebrafish model, revealing that the microcapsules did not alter the locomotor activity and were not toxic within 96 h by oral administration, suggesting their biological safety. In vitro cytotoxic activity against HL-60 cells confirmed an IC

The success of cloning by somatic cell nuclear transfer depends on the efficiency of nuclear reprogramming, with the cycle stage of the donor cell playing a crucial role. Therefore, the aim was to evaluate three different approaches for cell cycle synchronization: (i) serum starvation (SS) for 1 to 4 days, (ii) contact inhibition (CI) for 1 to 3 days, and (iii) using cell cycle regulatory inhibitors (dimethyl sulfoxide, cycloheximide, cytochalasin B, or 6-dimethylaminopurine) for 1 and 2 days, in terms of their effects on synchronization in G0/G1 phases and viability of collared peccary skin fibroblasts. Flow cytometry analysis revealed that SS for 4 days (79.0% ± 1.6) and CI for 3 days (78.0% ± 1.4) increased the percentage of fibroblasts in G0/G1 compared to growing cells GC (68.1% ± 8.6). However, SS for 3 and 4 days reduced the viability evaluated by differential staining (81.4% ± 0.03 and 81.6% ± 0.06) compared to growing cells (GC, 95.9% ± 0.06). CI did not affect the viability at any of the analyzed time intervals. No cell cycle inhibitors promoted synchronization in G0/G1. These results indicate that CI for 3 days was the most efficient method for cell cycle synchronization in peccary fibroblasts.

The genus Phyllanthus belongs to the family Phyllanthaceae with large global distribution, with about 833 species, including Phyllanthus amarus and P. niruri. These species are widely used in traditional medicine because of their pharmacological potential. The objective of this work is to measure the potential of genus Phyllanthus after a technological and scientific monitoring to quantify and evaluate publications and patents related to Phyllanthus spp. with emphasis on P. amarus and P. niruri. The scientific monitoring summarizes morphotaxonomic, pharmacological, chemical, ethnomedicinal and biological aspects. The research was carried out based on papers found in journals deposited in the Web of Science and NCBI (PUBMED) databases and on patents found in the European Patent Office (ESPACENET), Google Patents and the National Institute of Industrial Property (INPI). The results show strong interest in the areas of Pharmacology and Medicinal Chemistry. Patents fall within the Human Necessities section by International Patent Classification as preparations for Medical, Dental or Hygienic Purposes. The summary of monitoring analysis demonstrates the potential pharmacological potential of P. amarus and P. niruri as agents to treat different types of diseases and a range of possibilities for clinical trials in several areas of health.

Brown propolis from northern Ceara, Brazil, was found to contain predominantly sesquiterpenes in its volatile profile. The ethanolic propolis extract yielded a substantial apolar fraction (80.07 ± 1.47%) after liquid–liquid partitioning, which explains the low phenolic content (41.33 ± 1.68 mgGAE gEXT−1). Phenolics, such as p-coumaric (0.13 ± 0.04 mg gEPE−1), ferulic (1.07 ± 0.09 mg gEPE−1), and trans-cinnamic (0.41 ± 0.02 mg gEPE−1) acids, were detected in the EtOH-soluble extract. The apolar fraction was rich in triterpenes such as cycloartenol (12.85 ± 2.80%), α-amyrenyl acetate (4.37 ± 0.69%), and α-amyrin (3.89 ± 0.62%). Despite the lack of a direct antibacterial activity against Staphylococcus aureus 1199-B, both fractions exhibited potentiating effects in combination with norfloxacin; these effects could be attributed to efflux pump inhibition. The apolar fraction was more effective than the EtOH-soluble one at reducing the minimum inhibitory concentration, producing similar results to chlorpromazine and ethidium bromide. The EtOH-soluble fraction exhibited cytostatic properties at lower concentrations, while the apolar fraction demonstrated better selectivity for PC3 and HL60 tumor cells. The findings highlight the biological potential of Brazilian brown propolis for application as a complementary agent in the treatment of S. aureus infections and as an alternative therapy for cancer treatment.

Miconia is the largest genus of the flowering plant family Melastomataceae and is widely distributed in the American continent. However, despite its size and widespread distribution, there are few studies on its phytochemical composition and biological activities. Therefore, the aims of this study were to isolate and identify the constituents of Miconia burchellii Triana (Melastomataceae) leaves, and assess their in vitro antiproliferative activity. Phytochemical study allowed the characterization of eight compounds: pheophorbide A ethyl ester (1), kaempferol (2), kaempferol-3-O-β-glucopyranoside (3), kaempferol-3-O-β-galactopyranoside (4), oleanolic acid (5), ursolic acid (6), lupeol (7) and β-sitosterol (8). The ethyl acetate fraction showed potent cytotoxic activity against four of five tumor cell lines tested and compound (1) was cytotoxic against leukemia cell lines (IC50 4.74 μg mL−1), although neither the fraction nor the compound (1) showed selectivity between tumor and non-tumor lines. To the best of our knowledge this is the first study to report on the chemical composition and biological activity of M. burchellii and this is the first case in which cytotoxic activity is attributed to pheophorbide A ethyl ester.

Made available in DSpace on 2021-06-25T10:47:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-02-01 Casearia sylvestris is an outstanding representative of the Casearia genus. This representability comes from its distinctive chemical profile and pharmacological properties. This species is widespread from North to South America, occurring in all Brazilian biomes. Based on their morphology, 2 varieties are recognized: C. sylvestris var. sylvestris and C. sylvestris var. lingua. Despite the existence of data about their chemical composition, a deeper understanding of the specialized metabolism correlation and variation in respect to environmental factors and its repercussion over their biological activities was still pending. In this study, an UHPLC-DAD-based metabolomics approach was employed for the investigation of the chemical variation of 12 C. sylvestris populations sampled across 4? Brazilian biomes and ecotones. The correlation between infraspecific chemical variability and the cytotoxic and antioxidant activities was achieved by multivariate data analysis. The analyses showed that C. sylvestris var. lingua prevailed at Cerrado areas, and it was correlated with lower cytotoxic activity and high level of glycosylated flavonoids. Among them, narcissin and isorhamnetin-3- O-α -L-rhamnopyranosyl-(1 → 2)- α -L-arabinopyranoside showed good correlation with the antioxidant activity. Conversely, C. sylvestris var. sylvestris prevailed at the Atlantic Forest areas, and it was associated with high cytotoxic activity and high content of clerodane diterpenoids. Different casearins showed good correlation (R 2= 0.3?-?0.70) with the cytotoxic activity. These findings highlighted the great complexity among different C. sylvestris populations, their chemical profile, and the related biological activities. Consequently, it can certainly influence the medicinal properties, as well as the quality and efficacy, of C. sylvestris phytomedicines. Institute of Chemistry Department of Biochemistry and Organic Chemistry São Paulo State University (UNESP), CEP 14800-060, Rua Prof. Francisco Degni 55 Natural Products Laboratory Institute of Biology Leiden University Natl. Inst. of Alternative Technol. for Detection Toxicological Assess. Removal of Micropollutants and Radioactive Substances Araraquara Agronomic Institute of Campinas Herbarium IAC Department of Biophysics and Physiology Laboratory of Experimental Cancerology Federal University of Piauí Department of Physiology and Pharmacology Faculty of Medicine Federal University of Ceará Institute of Chemistry Department of Biochemistry and Organic Chemistry São Paulo State University (UNESP), CEP 14800-060, Rua Prof. Francisco Degni 55

In the present work, we investigated the minimal inhibitory concentration (MIC) against fungal strains (Fonsecaea pedrosoi, Microsporum canis, Candida albicans, Cryptococcus neoformans), and cytotoxicity to normal cell lines for modified red angico gum (AG) with eterifying agent N-chloride (3-chloro-2-hydroxypropyl) trimethylammonium (CHPTAC). Quaternized ammonium groups were linked to AG backbone using N-(3-chloro-2-hydroxypropyl) trimethylammonium chloride. The chemical features of the quaternized gum derivatives (QAG) were analyzed by: FTIR, elemental analysis, Zeta potential and gel permeation chromatography. The angico quaternizated gum presented a degree of substitution (DS) of 0.22 and Zeta potential of +36.43. For the antifungal test, it was observed that unmodified gum did not inhibit fungal growth. While, QAG inhibited the growth of most fungi used in this study. By AFM technique QAG interacted with the fungal surface, altering wall roughness significantly. The probable affinity of fragments of the QAG structure for the fungal enzyme 5I33 (Adenylosuccinate synthetase) has been shown by molecular docking. Low cytotoxicity was observed for polymers (unmodified gum and QAG). The results demonstrate that the quaternized polymer of AG presented in this study is a quite promising biomaterial for biotechnological applications.

This paper explores the application of cashew gum (CG) as an in vitro antiproliferative, firstly by isolating and characterizing the gum using elemental analysis, gel-permeation chromatography, nuclear magnetic resonance (NMR) and atomic force microscopy (AFM). The molar mass of isolated CG was in the order of 103–104 g/mol, with small protein traces present. Polymer characterization by NMR identified key signals correlating to galactose, glucose, rhamnose and acid-related groups. Three distinct conformational stages were observed by AFM. The impact of CG on cell morphology and viability with both tumor and non-tumor cell lines was studied by AFM and 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay respectively. Antiproliferative activity was confirmed for HCT116 (colorectal carcinoma), B16F10 (melanoma) and HL60 (promyelocytic leukemia) cancer cell lines. A change in cell morphology was demonstrated as an increased surface roughness for HL60. Considering that a CG does not exhibit cytotoxicity to non-tumor lines, it can be seen that the CG shows selectivity for tumor cells and can be a promising biomaterial for future studies.

Double ruthenium(II)-catalyzed alkyne annulations of quinones were accomplished. Thus, a strategy is reported that provides step-economical access to valuable quinones with a wide range of applications. C-H/N-H activations for alkyne annulations of naphthoquinones provided challenging polycyclic quinoidal compounds by forming four new bonds in one step. The singular power of the thus-obtained compounds was reflected by their antileukemic activity.

[Image: see text] Synthetically derived samples of (+)-(6aS,11aS)-2,3,9-trimethoxypterocarpan [(+)-1] and its enantiomer [(−)-1], both of which are examples of naturally occurring isoflavonoids, were evaluated, together with the corresponding racemate, as cytotoxic agents against the HL-60, HCT-116, OVCAR-8, and SF-295 tumor cell lines. As a result it was established that compound (+)-1 was particularly active with OVCAR-8 cells being the most sensitive and responding in a dose-dependent manner. A study of cell viability and drug-induced morphological changes revealed the compound causes cell death through a mechanism characteristic of apoptosis. Finally, a computational study of the interactions of compound (+)-1 and (S)-monastrol, an established, synthetically derived, potent, and cell-permeant inhibitor of mitosis, with the kinesin-type protein Eg5 revealed that both bind to this receptor in a similar manner. Significantly, compound (+)-1 binds with greater affinity, an effect attributed to the presence of the associated methoxy groups.

Triethylphosphinegold(I) complexes [Au(HL1)P(CH2CH3)3]PF6 (1), [Au(HL2)P(CH2CH3)3]PF6 (2), and [Au(HL3)P(CH2CH3)3]PF6 (3) were obtained with (E)-2-(1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ylidene)hydrazinecarbothioamide (HL1), (E)-N-methyl-2-(1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ylidene)hydrazinecarbothioamide (HL2), and (E)-2-(1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ylidene)-N-phenylhydrazinecarbothioamide (HL3). All compounds were assayed for their cytotoxic activities against HCT-116 colorectal carcinoma cells under normoxia and hypoxia conditions and against nonmalignant HEK-293 human embryonic kidney cells under normoxia conditions. The thiosemicarbazone ligands HL1-HL3 were inactive against HCT-116 cells under hypoxia but while HL3 was inactive, HL1 and HL2 proved to be cytotoxic to both cell lineages under normoxia conditions. Complexes (1-3) and the triethylphosphinegod(I) precursor proved to be active against both cell lineages in normoxia as well as in hypoxia. While 1 and 3 revealed to be active against HEK-293 and HCT-116 cells, being approximately as active against HCT-116 cells in normoxia as under hypoxia, complex (2) proved to be more active against HCT-116 cells under hypoxia than under normoxia conditions, and more active against HCT-116 cells than against the nonmalignant HEK-293 cells, with the selectivity index, calculated as SI = IC50HEK-293/IC50HCT-116hypoxia, equal to 3.7, similar to the value obtained for the control drug tirapazamine (tirapazamine (TPZ), SI = 4). Although the compounds showed distinct cytotoxic activities, the electrochemical behaviors of HL1-HL3 were very similar, as were the behaviors of complexes (1-3). Complex (2) deserves special interest since it was significantly more active under hypoxia than under normoxia conditions. Hence, in this case, selective reduction of the nitro group in a low oxygen pressure environment, resulting in toxic reactive oxygen species (ROS) and damage to DNA or other biomolecules, might operate, while for the remaining compounds, other modes of action probably occur.

In this work, eight chalcones were synthesized from the 2-hydroxy-3,4,6trimethoxyacetophenone isolated from Croton anisodontus with benzaldehyde and its derivatives as well as evaluated its cytotoxic and antifungal activities. Chalcones were synthesized by the Claisen-Schimdt aldol condensation reaction in basic medium and identified by 1H and 13C NMR, IR and MS. The MTT assay was used to determine the cytotoxicity of all synthetized compounds against human cancer cell lines. The results showed that the % RCV varied from 19.43 ± 1.31 to 75.51 ± 1.84 %. The chalcone (E)-3-(4-fluorophenyl)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)prop-2-en-1-one demonstrated the strongest activity against HCT-116 cells (% RCV = 75.51 ± 1.84). The in vitro antifungal potential of the chalcones showed that chalcones (E)-3-(furan-2-yl)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)prop-2-en-1-one (MIC 0,625 mg/mL against C. albicans LABMIC 0105) and (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (MIC 0,312 mg/mL against C. albicans LABMIC 0107) were considered as chalcones of better fungal inhibition. The synergistic evaluation in vitro showed no synergistic effect for both chalcones and for kinetics of fungal death, only treatment with chalcone (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one against LABMIC 0107 was able to promote reduction of fungal cells between the periods of 4 to 8 h and 100% inhibition thereafter, resembling the mechanism of action of Amphotericin B.

O PRESENTE ARTIGO TEM COMO OBJETIVO ANALISAR COMO AS ATIVIDADES DE LEITURA DOS TEXTOS MULTIMODAIS DO LIVRO DIDÁTICO DE PORTUGUÊS DO 2º ANO DO ENSINO FUNDAMENTAL EXPLORAM O ENSINO DA LEITURA MULTIMODAL DE MANEIRA QUE CONTRIBUAM PARA O LETRAMENTO MULTIMODAL. PARA ISSO, SELECIONAMOS OS TEXTOS MULTIMODAIS VERBO-VISUAIS PRESENTES NO LIVRO DIDÁTICO DE PORTUGUÊS PARA ANÁLISE, OBSERVAMOS AS ATIVIDADES DE LEITURA DOS TEXTOS SELECIONADOS E ANALISAMOS COMO AS ATIVIDADES DE LEITURA CONTRIBUEM PARA DESENVOLVER AS CAPACIDADES LEITORAS ESPECÍFICAS PARA O LETRAMENTO MULTIMODAL. ESSA INVESTIGAÇÃO É CARACTERIZADA COMO UMA PESQUISA-AÇÃO DE CUNHO DESCRITIVO-ANALÍTICO, ADOTANDO UMA METODOLOGIA DE ABORDAGEM QUALITATIVA. POR FIM, PODEMOS CONCLUIR QUE ESSA PESQUISA IRÁ CONTRIBUIR PARA A MELHORIA DO ENSINO, POIS INCENTIVARÁ OS PROFESSORES A EXPLORAREM OS TEXTOS MULTIMODAIS, DESENVOLVENDO HABILIDADES NA LEITURA DESSES TEXTOS PELOS ALUNOS DE MANEIRA MAIS ABRANGENTE E ENRIQUECEDORA, POSSIBILITANDO SUA INTERAÇÃO EM DIFERENTES AMBIENTES SOCIAIS AO UTILIZAREM DIFERENTES LINGUAGENS DE FORMA SIGNIFICATIVA E COERENTE.

The genus Chamaecrista comprises more than 330 species, with only a few studies on their chemical composition and biologic activities. In this study, the phytochemical profile of leaf, stems, and fruits extracts of the C. duckeana were examined by UPLC-ESI-HRMS analysis to determine possibly bioactive constituents. The antioxidant activity was carried out through in vitro assay, by the sequestration of the free radical DPPH. To evaluate the cytotoxic activity of the extracts, an MTT assay was used and the IC50 was determined against HL60 and RAJI cell lines. The metabolic profiles of the botanical parts are dominated by flavonoid class, highlighting isoflavonoids such as daidzin and ononin. All these compounds are reported for the first time in C. duckeana. The extracts presented antioxidant potential, and the activity of the stems extract was higher than the standard butylated hydroxytoluene. In the cytotoxic assay, only HL60 line (leukemia) had growth inhibition over 80%. The stems presented more expressive cytotoxicity with IC50 of 137.3 (104.6-180.1) and 106.8 (96.52-118.3) μmol. L-1 for HL60 and RAJI, respectively. In conclusion, the present work provides an in-depth knowledge about the chemical profile of C. duckeana, a species rich in bioactive secondary metabolites with cytotoxic activity

Mucilage extracted from chia seed (Salvia hispanica L.) (MCHs) has come to prominence in recent studies due to its attractive biological activities, improving the interest in developing Salvia hispanica as an industrial crop for sustainable source of bioactive polysaccharide. In this work, chia mucilage properties were evaluated, including physicochemical, photostability, cytocompatibility, and mucoadhesion characteristics. MCHs exhibited excellent photostability, with a degradation percentage of 6.6 % after 120 min under UV light. MTT assay results showed excellent cytocompatibility of MCHs on the L929 fibroblast cell line and additionally, the biomaterial showed promising mucoadhesive activity. Overall, the knowledge of these new properties of chia mucilage reinforces the multipotential feature of this biopolymer for application in food, cosmetic and pharmaceutical industries.

We report the synthesis of 47 new quinone-based derivatives via click chemistry and their subsequent evaluation against cancer cell lines and the control L929 murine fibroblast cell line. These compounds combine two redox centers, such as an ortho-quinone/para-quinone or quinones/selenium with the 1,2,3-triazole nucleus. Several of these compounds present IC(50) values below 0.5 μM in cancer cell lines with significantly lower cytotoxicity in the control cell line L929 and good selectivity index. Hence, our study confirms the use of a complete and very diverse range of quinone compounds with potential application against certain cancer cell lines.

Este artigo tem como objetivo analisar a implementação de uma política habitacional na Reserva Extrativista Marinha Caeté-Taperaçu (REMCT), localizada no município de Bragança, no estado do Pará, a qual nos permite observar como a precariedade das construções habitacionais podem ampliar as desigualdades e resultar em desdobramentos que afetam a qualidade de vida. O Crédito Habitacional foi responsável pela construção de habitações destinadas aos moradores da REMCT no período de 2005 a 2013. Embora tenha ocorrido em um período considerável para sua implementação, a política pública não foi capaz de alcançar nem 30% do total de pessoas que foram cadastradas. Une-se a isso os reclamos dos moradores da RESEX sobre a precariedade nas construções das moradias, sem levar em conta as necessidades laborais e ambientais, requeridas pelo território, ocupado majoritariamente por extrativistas marinhos. Outro fator reverso, foi a interrupção dos recursos destinados ao INCRA, órgão financiador do Crédito Habitacional, aprofundando o déficit de condições de vida. Para esta análise de cunho qualitativo, efetuou-se levantamento bibliográfico sobre Reservas Extrativistas Marinha, políticas públicas, políticas habitacionais e desigualdade e Amazônia; foram realizadas entrevistas semiestruturadas com moradores da Resex; e levantamento de dados em sites e plataformas oficiais. A partir dos resultados, percebemos que a política habitacional possui caráter ambíguo, por um lado, tem produzido satisfação material entre seus proprietários, mas também, por não alcançar a todos os necessitados, pode vir a contribuir para o acirramento de desigualdades.

Phytochemical investigation of the atemoya aerial parts was carried out by LC-MS-IT and cytotoxic activities were evaluated as well. These results led to the identification of a new N-oxide alkaloid (dehydroanomuricine-N-oxide) and eight other alkaloids: scoulerine, reticuline, isocorydine, norisocorydine, asimilobine, nornuciferine, anonaine, and liriodenine. The new alkaloid dehydroanomuricine-N-oxide and anomuricine were also isolated. The structures of these compounds were determined by spectroscopic and spectrometric techniques. The cytotoxic capacity of crude methanolic extract and the alkaloidal fraction were evaluated, showing moderate cytotoxicity. The isolation and identification of these alkaloids are an important contribution to the chemotaxonomy of the genus Annona and the Annonaceae family.

SUMMARY Introduction: Recent research has reported the cytotoxic potential of hydrazones against various strains of cancer cells. Aim: To evaluate the anticancer activity in vitro and the pharmacokinetic profile of six synthesized hydrazonic compounds, identified as vanillin 1-phthalazinylhydrazone (VAN-1); 2,4-dinitrophenylhydra-zone vanillin (VAN-2); phenylhydrazone cinnamaldehyde (CIN-1); isonicotinoyl hydrazone cinnamaldehyde (CIN-2); cinnamaldehyde 1-phthalazinylhydrazone (CIN-3); and 2,4-dinitrophenylhydrazone cinnamaldehyde (CIN-4). The cytotoxic activity was evaluated against four strains of cancer cells. Methodology: The pharmacokinetic parameters of absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of the hydrazones were evaluated using the PreADMET program. Results: Hydrazones derived from cinnamaldehyde (CIN-1 and CIN-2) showed high cytotoxic activity against leukemic (HL-60) and glioblastomas (SF-295) cell lines. The pharmacokinetic profile of the hydrazones showed that, in general, the hydrazones presented satisfactory characteristics of ADME/T. In addition, it was observed that CIN-2 presented the most promising in silico profile, showing high intestinal absorption, desirable distribution profile related to plasma protein binding, adequate renal excretion, and low toxicity. The ADME/T profile of the CIN-1 compound highlighted its potential as a promising antineoplastic agent with action of the CNS, more specifically against glioblastomas. RESUMEN Introducción: Investigaciones recientes han informado del potencial citotóxico de las hidrazonas contra varias líneas de células cancerosas. Objetivo: Evaluar la actividad anticancerígena in vitro y el perfil farmacocinético de seis compuestos hidrazónicos sintetizados, identificados como vainillina 1-ftalazinilhidrazona (VAN-1); vainillina 2,4-dinitrofenilhidrazona (VAN-2); fenilhidrazona cinamal-dehído (CIN-1); cinamaldehído de isonicotinoil hidrazona (CIN-2); cinamalde-hído 1-ftalazinilhidrazona (CIN-3); y 2,4-dinitrofenilhidrazona cinamaldehído (CIN-4). Se evaluó la actividad citotóxica frente a cuatro líneas celulares cancerosas. Metodología: Los parámetros farmacocinéticos de absorción, distribución, metabolismo, excreción y toxicidad (ADME/T) de las hidrazonas se evaluaron mediante el programa PreADMET. Resultados: Las hidrazonas derivadas del cinamaldehído (CIN-1 y CIN-2) mostraron una alta actividad citotóxica contra las líneas celulares leucémicas (HL-60) y glioblastomas (SF-295). El perfil farmacocinético de las hidrazonas mostró que, en general, las hidrazonas mostraban características satisfactorias de ADME/T. Además, se observó que CIN-2 presentó el perfil in silico más prometedor, presentando alta absorción intestinal, perfil de distribución deseable relacionado con la unión a proteínas plasmáticas, excreción renal adecuada y baja toxicidad. El perfil ADME/T del compuesto CIN-1 destacó su potencial como agente antineoplásico prometedor con acción sobre el SNC, más específicamente contra los glioblastomas. RESUMO Introdução: Pesquisas recentes relataram o potencial citotóxico das hidrazonas contra várias linhagens de células cancerígenas. Objetivo: Validara atividade anti-câncer in vitro e o perfil farmacocinético de seis compostos hidrazônicos sintetizados, identificados como vanilina 1-ftalazinil-hidrazona (VAN-1); vanilina 2,4-dinitrofenil-hidrazona (VAN-2); cinnamaldeído de fenil-hidrazona (CIN-1); cinamaldeído isonicotinoil-hidrazona (CIN-2); 1-ftalazinil-hidrazona de cinnamaldeído (CIN-3); e cinamaldeído de 2,4-dinitrofenil-hidrazona (CIN-4). A atividade citotóxica foi avaliada contra quatro linhagens de células cancerígenas. Metodologia: Os parâmetros farmacocinéticos de absorção, distribuição, metabolismo, excreção e toxicidade (ADME/T) das hidrazonas foram avaliados utilizando o programa PreADMET. Resulados: As hidrazonas derivadas do cinnamaldeído (CIN-1 e CIN-2) apresentaram alta atividade citotóxica contra as linhagens celulares leucêmicas (HL-60) e de glioblastomas (SF-295). O perfil farmacocinético das hidrazonas mostrou que, em geral, as hidrazonas apresentaram características satisfatórias de ADME/T. Além disso, observou-se que a CIN-2 apresentou o perfil in silico mais promissor, exibindo alta absorção intestinal, perfil de distribuição desejável relacionado à ligação às proteínas plasmáticas, excreção renal adequada e baixa toxicidade. O perfil ADME/T do composto CIN-1 destacou seu potencial como um agente antineoplásico promissor com ação do SNC, mais especificamente contra glioblastomas.

The imprinted H19 long non-coding RNA, a knowing oncofetal gene, presents a controversial role during the carcinogenesis process since its tumor suppressor or oncogenic activity is not completely elucidated. Since H19 lncRNA is involved in many biological pathways related to tumorigenesis, we sought to develop a non-cancer lineage with CRISPR-Cas9-mediated H19 knockdown (H19-) and observe the changes in a cellular context. To edit the promoter region of H19, two RNA guides were designed, and the murine C2C12 myoblast cells were transfected. H19 deletion was determined by DNA sequencing and gene expression by qPCR. We observed a small deletion (~ 60 bp) in the promoter region that presented four predicted transcription binding sites. The deletion reduced H19 expression (30%) and resulted in increased proliferative activity, altered morphological patterns including cell size and intracellular granularity, without changes in viability. The increased proliferation rate in the H19- cell seems to facilitate chromosomal abnormalities. The H19- myoblast presented characteristics similar to cancer cells, therefore the H19 lncRNA may be an important gene during the initiation of the tumorigenic process. Due to CRISPR/Cas9 permanent edition, the C2C12 H19- knockdown cells allows functional studies of H19 roles in tumorigenesis, prognosis, metastases, as well as drug resistance and targeted therapy.

Tellurium is a rare element that has been regarded as a toxic, nonessential element, and its biological role is not clearly established. In addition, the biological effects of elemental tellurium and some of its organic and inorganic derivatives have been studied, leading to a set of interesting and promising applications. Diphenyl ditelluride (DPDT), an organic tellurium derivate, showed antioxidant, antigenotoxic, antimutagenic, and anticancer properties. The antioxidant and prooxidant properties of DPDT are complex and depend on experimental conditions, which may explain the contradictory reports of these properties. In addition, DPDT may exert its effects through different pathways, including distinct ones to those responsible for chemotherapy resistance phenotypes: transcription factors, membrane receptors, adhesion, structural molecules, cell cycle regulatory components, and apoptosis pathways. This review aims to present recent advances in our understanding of the biological effects, therapeutic potential, and safety of DPDT treatment. Moreover, original results demonstrating the cytotoxic effects of DPDT in different mammalian cell lines and systems biology analysis are included, and emerging approaches for possible future applications are inferred.

14 new naphthoquinones were prepared and tested against human cancer cell lines PC-3 (prostate), HCT-116 (colon carcinoma), SNB-19 (glioblastoma), HL-60 (leukemia) and MCF-7 (breast), and a nontumor cell line L929 (murine fibroblasts) to determine cytotoxicity with the MTT assay. 8-OH-β-lapachones (14a, 14c, 14d) presented best results, showing low IC50 values and high selectivity for HCT-116 and HL-60 tumor cells.

Natural products are a very productive leading source of compounds for the development of medicines. The aim of this research was to investigate the in vitro antiproliferative and antileishmanial activities of 21 extracts from 7 Asteraceae species. Dried aerial parts of Asteraceae plant species were extracted using organic solvents in order of increasing polarities. Antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, and nine extracts (43%) displayed moderate to high in vitro antiproliferative activity against human cancer cell lines HCT-116, OVCAR-8 and SF-295. Two crude extracts displaying antiproliferative activity were fractionated and yielded a fraction rich in lupeol acetate, a fraction rich in lupeol and 5,7,3′,4′-tetrahydroxyflavone-7-O-β-D-glucopyranoside. The antileishmanial activity was evaluated by amastigotes growth inhibition test in Leishmania amazonensis, and three extracts showed promising activity. Phytochemical screening of all plant extracts was also made for terpenoids, flavonoids, tannins, alkaloids and saponins.

Cancer is a health problem affecting a large part of the world population. In this context, several research groups have investigated molecules with higher efficiency and lower side effects. The species Leonotis nepetifolia is a shrub belonging to the Lamiaceae family with cytotoxicity activity reported in literature. This paper describes the isolation of compounds hentriacontane, phytyl palmitate, stigmasteryl glucoside, 6,7-dimethoxy-5,3’,4’trihidroxyflavone, apigenin-7-O-glucoside and luteolin-7-O-glucoside from extracts and the chemical composition of essential oil from the leaves of Brazilian L. nepetifolia species in addition to its in vitro cytotoxic activities. All compounds were identified by a series of spectrometric and spectroscopic methods, mainly NMR (1D and 2D) and GC-MS, as well as by comparison with literature data. The cytotoxic activity of isolated compounds and essential oil was performed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, against tumor cell lines HCT-116 (human colon) and SF-295 (glioblastoma). The alcohol 1-octen-3-ol was the majoritary compound of the essential oil and the compounds hentriacontane, phytyl palmitate, stigmasteryl glucoside, apigenin-7-O-glucoside and luteolin-7-O-glucoside were describes for the first time in this species. All compounds tested and essential oil showed low cytotoxic activity for the cell lines tested, suggesting that other phytochemical studies should be conducted for the discovery of compounds responsible by cytotoxic activity of the species.

The study aimed to evaluate cytotoxicity and antitumor activity of perillaldehyde 1,2-epoxide (PE), a p-menthane monoterpene derivative against four human tumor cell lines ovarian cancer (OVCAR-8), colon carcinoma (HCT-116), glioblastoma (SF-295) and leukemia (HL-60) using the colorimetric MTT assay. PE showed a high degree of inhibition of cell proliferation (GI = 95.66 to 99.71%) and IC50 16.14 μM (± 1.86), 23.61 μM (± 1.13), 21.99 μM (± 2.64) and, 9.70 μM (± 1.01) against tumor cells, respectively. Then, in vivo antitumor activity of the PE was assessed in sarcoma 180-bearing mice. Tumor growth inhibition rates were 33.4, 56.4 and 66.6% at doses of 100 and 200 mg/kg/day for the PE and 25 mg/kg/day for 5-FU intraperitoneal treatments, respectively. Toxicological effects related to the spleen, kidneys, liver, and hematological were investigated in mice submitted to treatment. Furthermore, histopathological analyses of these organs were absent of any morphological changes in the animals treated with PE. The viability of HL-60 cells was affected by perillaldehyde 1, 2-epoxide after an exposure period of 72 h when analyzed by trypan blue exclusion. PE reduced the number of viable cells associated with an increase in non-viable cells, which contributes to the increased number of dead cells in the morphological analysis. The incorporation of ethidium bromide/acridine orange, the treated cells suggests cytotoxicity via apoptosis and necrosis. So on the results, we conclude that PE presents cytotoxic and antitumoral activity through apoptotic and necrotic processes. Key words: Essential oils, p-menthanes, natural products, cytotoxicity, antitumor activity, sarcoma 180.

The use of co-products from the fruit agroindustry as a source of bioactive molecules presents economic advantages, since these compounds are highly available and inexpensive. Therefore, the present study aimed to evaluate their qualitative chemical composition followed by multivariate analysis, and to correlate the results with those of the cytotoxicity tests. The non-polar metabolic profiles of the leaves of seven commercial pineapple (Ananas comosus (L.) Merr.) cultivars were investigated by using GC–MS. Twenty-seven metabolites were identified from the seven hexanic extracts. Multivariate analysis (Hierarchical Cluster Analysis, Principal Component Analysis and Partial Least Squares) revealed significant differences in the metabolic fingerprint of the different cultivars. Overall, the hexanic extracts of the seven cultivars of pineapple leaves showed promising antitumor activity against the six tumor lines tested (colon, leukemia, prostate, astrocytoma, breast and cervix). Correlation of the chemometric data, qualitative analysis, and cytotoxic tests allowed us to determine the possible biomarkers responsible for each specific antitumor activity. This study demonstrates a great valuation potential of a co-product little explored in the agroindustry of foods through the prospection of biologically active compounds.

A simple and fast methodology under microwave irradiation for the synthesis of 2-aminopyrimidine and pyrazole derivatives using Atwal reaction is reported. After the optimization of the reaction conditions, eight 2-aminolpyrimidines containing ferrocene and heterocycles and three ferrocene pyrazoles were synthesized from the respective chalcones in good yields. Eight compounds had their structure determined by X-ray diffraction. The molecular hybrid 6a-h and 9a-c were tested on four cancer cell lines - HCT116, PC3, HL60 and SNB19 - where four pyrimidine 6a, 6f-h and one pyrazole 9c derivatives show promising antiproliferative activity. In addition, docking simulation and machine learning methods were carried out to explain the biological activity achieved by the synthetized compounds.