Bioguided Fractionation of Phyllanthus spp.: Unveiling Anticancer Potential through Metabolomic Correlation and ADMETox Insights.

Cancer remains a significant global health concern, with mortality rates steadily rising and prompting an urgent search for effective treatments. This study focuses on the medicinal properties of plants from the Phyllanthus genus, specifically Phyllanthus amarus and Phyllanthus niruri, which have shown promise in traditional medicine. Through bioguided fractionation using preparative high-performance liquid chromatography (HPLC), bioactive compounds were isolated and identified using ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-QTOF-MSE) and nuclear magnetic resonance (NMR) spectroscopy. Chemometric analyses such as principal component analysis (PCA) aided in understanding metabolite distribution. Biological assays demonstrated cytotoxic activities of specific fractions against cancer cell lines, notably the PhyN 4n fraction from P. niruri, which induced S-phase cell cycle arrest and apoptosis in HL60 cells. These findings underscore the anticancer potential of Phyllanthus species and lay the groundwork for future drug development efforts. The study's integration of advanced analytical techniques, chemometrics, and biological assays provides valuable insights for harnessing natural products in the fight against cancer.

Ethanolic extract from leaves of tithonia diversifolia induces apoptosis in HCT-116 cells through oxidative stress.

Tithonia diversifolia is a perennial bushy plant found in South America with significant ethnopharmacological importance as an antimalarial, antidiabetic, antibacterial, and anticancer agent. The aim of the present study was to determine the cytotoxicity of the ethanolic extract from leaves of T. diversifolia (TdE) on human cancer cell lines (HCT-116, SNB-19, NCIH-460 and MCF-7), as well as the mechanism of action involved in cell death and cellular modulation of oxidative stress. The TdE exhibited significant activity with IC50 values ranging from 7.12 to 38.41 µg/ml, with HCT-116 being the most sensitive cell line. Subsequent experiments were conducted with HCT-116 cell line. TdE decreased the number of viable cells, followed by induction of apoptotic events, increase in mitochondrial membrane permeabilization, and enhanced G2/M phase of the cell cycle. Pro-oxidative effects including elevated acidic vesicular organelle formation, lipid peroxidation, and nitric oxide by-products, as well as reduced levels of intracellular glutathione and reactive oxygen species production were also observed following incubation with TdE, which may lead to DNA damage followed by apoptotic cell death. These results demonstrate the potential of TdE ethanolic leaf extraction for biological activity and enhance the importance of continuing to study natural sources of plants for the development of anticancer agents.

Fatty acid intake and prevalence of depression among Brazilian graduates and postgraduates (CUME Study).

BACKGROUND: Dietary fatty acids are related to the development of several inflammatory-related diseases, which may include depression. So, the association between fatty acids, culinary oils and fat intake and depression in highly educated Brazilians was evaluated. METHODS: Multicenter cross-sectional study using baseline data from the Cohort of Universities of Minas Gerais. The diagnosis of depression was self-reported, and the daily intake of fatty acids was assessed using a 144-item food frequency questionnaire (FFQ). RESULTS: A total of 7157 participants (68.83 % women) with a median age of 33 years were included. The prevalence of depression was 12.60 % (N = 902). In the adjusted analyses, it was observed that individuals with the highest intake of omega-6 fatty acids (n-6) (OR: 1.36, 95 % CI 1.11-1.67) had a higher prevalence of depression. This increased n-6 intake was identified as a risk factor for depression only among male participants, while among overweight participants, higher n-6 intake was also positively associated with depression. Conversely, a higher ratio of polyunsaturated to monounsaturated and saturated fatty acids (PM/S) was also found to be positively associated with depression, but this association was observed only among non-overweight participants. No associations were found between the consumption of culinary oils or fats and depression. LIMITATIONS: Cross-sectional design limits the assessment of causality. The use of the FFQ can make estimates more difficult. CONCLUSION: Higher consumption of n-6, and higher PM/S ratios were associated with depression, and individual factors can interfere. The mental health care policies should include specific nutritional strategies.

SARS CoV-2 infection among Healthcare Workers from different public health units in Brazil.

Understanding COVID-19 exposure differences among Healthcare Workers (HCWs) across various healthcare units is crucial for their protection and effective management of future outbreaks. However, comparative data on COVID-19 among HCWs in different healthcare units are scarce in Brazil. This study evaluated the relationship between SARS-CoV-2 infection and workplaces in HCWs from three distinct healthcare settings in Brazil. It also examined COVID-19 symptom dynamics reported by them. The cohort comprised 464 HCWs vaccinated with two doses of CoronaVac and a BNT162b2 booster from different institutions: Primary Health Care Units (PHCUs), Emergency Care Units (ECUs), and Hospitals. Participants answered a questionnaire and underwent blood collection at various time points after vaccinations. RT-PCR data and post-vaccination antibody responses were utilized as indicators of SARS-CoV-2 infection. We found that most infected HCWs worked in ECUs, where positive RT-PCR percentages were higher compared to PHCUs and Hospitals. ECUs also showed the highest seropositivity and antibody levels, especially after the first CoronaVac dose. The second dose of CoronaVac diminished the differences in the antibody levels among HCWs from ECUS, PHCUs, and Hospitals, indicating the benefit of the second dose to equalize the antibody levels between previously exposed and unexposed persons. Moreover, COVID-19 symptoms appeared to evolve over time.

Antibody response following the fourth SARS-CoV-2 vaccine dose during the Omicron wave in Brazil.

We investigated the impact of the fourth dose with ChAdOx1 nCoV-19 (AstraZeneca) in the humoral immune response to SARS-CoV-2 during a 9-month follow-up period in which Omicron was the predominant variant in Brazil. IgG for the SARS-CoV-2 spike protein (S) and nucleocapsid (N) proteins were analyzed in samples collected before and after the fourth dose. All participants were tested monthly for SARS-CoV-2 infection by RT-qPCR. The antibody response induced by the fourth dose of the coronavirus disease 2019 vaccine was evaluated and compared with the response induced by the second and third doses. The additional antibody response to the viral S protein after the fourth dose was smaller than those after the third vaccine dose. In contrast, an increase in the N IgG levels could be observed after the fourth dose compared to other vaccine doses. In the comparison of the antibody response before and after the fourth dose, an increase in both S-and-N IgG was noted, mainly in the positive qPCR group. We did not observe a significant decline in IgG levels after the fourth dose, as observed after the second and third doses, therefore, a sustained humoral response to both S and N proteins seems to be achieved.

Naphth[1,2-d]imidazoles Bioactive from ß-Lapachone: Fluorescent Probes and Cytotoxic Agents to Cancer Cells.

Theranostics combines therapeutic and imaging diagnostic techniques that are extremely dependent on the action of imaging agent, transporter of therapeutic molecules, and specific target ligand, in which fluorescent probes can act as diagnostic agents. In particular, naphthoimidazoles are potential bioactive heterocycle compounds to be used in several biomedical applications. With this aim, a group of seven naphth[1,2-d]imidazole compounds were synthesized from ß-lapachone. Their optical properties and their cytotoxic activity against cancer cells and their compounds were evaluated and confirmed promising values for molar absorptivity coefficients (on the order of 103 to 104), intense fluorescence emissions in the blue region, and large Stokes shifts (20-103 nm). Furthermore, the probes were also selective for analyzed cancer cells (leukemic cells (HL-60). The naphth[1,2-d]imidazoles showed IC50 between 8.71 and 29.92 µM against HL-60 cells. For HCT-116 cells, values for IC50 between 21.12 and 62.11 µM were observed. The selective cytotoxicity towards cancer cells and the fluorescence of the synthesized naphth[1,2-d]imidazoles are promising responses that make possible the application of these components in antitumor theranostic systems.

Lemon gum: Non-toxic arabinogalactan isolated from Citrus × latifolia with antiproliferative property against human prostate adenocarcinoma cells.

Lemon gum (LG) obtained from Citrus × latifolia in Brazil was isolated and characterized. In addition, gum biocompatibility was evaluated in vitro and in vivo by Galleria mellonella and mice model. The cytotoxicity against tumor cells was also evaluated. The ratio of arabinose:galactose: rhamnose:4-OMe-glucuronic acid was 1:0.65:0.06:0.15. Small traces of protein were detected, emphasizing the isolate purity. Molar mass was 8.08 × 105 g/mol, with three different degradation events. LG showed antiproliferative activity against human prostate adenocarcinoma cancer cells, with percentage superior to 50 %. In vivo toxicity models demonstrated that LG is biocompatible polymer, with little difference in the parameters compared to control group. These results demonstrate advance in the study of LG composition and toxicity, indicating a potential for several biomedical and biotechnological future applications.

Antibody response 6 months after the booster dose of Pfizer in previous recipients of CoronaVac.

The most widely used vaccines were messenger RNA (mRNA), viral vector, and inactivated virus with two-dose schedules. In Brazil, the CoronaVac (Sinovac) was the first vaccine approved for emergency use, and the third dose was administered, preferably, with the BNT162b2 vaccine. We evaluated antibody levels after 6 months of the booster dose with BNT162B2 in previous recipients of CoronaVac and whether a subsequent severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection enhances the antibody response. We analyze the humoral response (spike [S] IgM for the SARS-CoV-2 and IgG for the S and nucleocapsid [N] proteins) in samples collected before the third dose and 6 months after the third dose. The presence of antibodies was measured by using Abbott Architect i2000SR. The IgM and IgG antispikes were stimulated mainly 30 days after the third dose (30d/3D), with a decline over time. The IgG anti-N was stimulated predominantly in 90d/3D and 180d/3D. The N IgG levels were 50 and 35 times higher in the positive polymerase chain reaction (PCR) group in 90d/3D and 180d/3D, respectively. The S IgG titers were 1.5 times elevated in the positive PCR group, in 180d/3D. The BNT162b2 boosted the S IgG levels, decreasing after 60 days. The booster shot induced IgM and IgG antibodies against spike protein. Infection after vaccination increased antibodies against protein N.

Flavonoids composition, antioxidant, anticholinesterase, and cytotoxic activities of flowers extract of Senna cearensis Afr. Fern.

The Senna genus has a wide diversity of species, with an interesting chemical composition of secondary metabolites and applications as medicine. The folk medicine, mainly in developing countries, uses species of Senna to treat seizures, epilepsy and constipation. Though the recognized bioactivity, some Brazilian native species of Senna remain unexplored, such as Senna cearensis, a native species of Caatinga. This is the first report about the bioactivity of the flowers of S. cearensis Afr. Fern., a native species of northeast Brazil. In this communication, flavonoids and catechins are identified in S. cearensis flowers and the chemical composition is linked with its antioxidant, anticholinesterase, and cytotoxic activities. By UPLC-QTOF, some compounds that belong to the class of flavonoids were identified. They are: catechin, epigallocatechin, guibourtinidol-(4α-8)-catechin, and cassiaflavan-(Cat)-epicatechin. The cytotoxic activity is more noticeable for the HL60 (leukemia) cell line with a cell growth inhibition (GI%) of 81.65 ± 5.65.

Chemical composition, in vitro cytotoxic and anticholinesterase activities of flower extracts of Senna spectabilis var. excelsa and Senna macranthera.

In this study, we investigated the phenolic and antioxidant content, cytotoxic, and anticholinesterase activities of flower extracts of Senna spectabilis var. excelsa and Senna macranthera. The antioxidant activities performed by the DPPH and ABTS methods showed that the extracts possess good antioxidant activity, with emphasis on the S. macranthera extract, which obtained results very similar to the rutin pattern. In the evaluation of the cytotoxic activity, the species S. spectabilis var. excelsa presented expressive cytotoxicity against the cellular lines PC3 and HL60 with IC50 values 21.08 and 31.37 µg mL-1, respectively. The results of anticholinesterase activity showed that both the plants induced enzyme inhibition, reaching 14 mm of inhibition in the case of S. spectabilis var. excelsa. The good results obtained in this work may be related to the presence of compounds such as apigenin-7-apioglucoside, quercetin 3,4'-diglucoside, cassine and spectaline identified in the extracts in our previous work.

COVID-19 in the Perioperative Period of Cardiovascular Surgery: the Brazilian Experience.

INTRODUCTION: We investigated the clinical course and outcomes of patients submitted to cardiovascular surgery in Brazil and who had developed symptoms/signs of coronavirus disease 2019 (COVID-19) in the perioperative period. METHODS: A retrospective multicenter study including 104 patients who were allocated in three groups according to time of positive real time reverse transcriptase-polymerase chain reaction (RT-PCR) for the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2): group 1, patients who underwent cardiac surgery > 10 days after positive RT-PCR; group 2, patients with a positive RT-PCR within 10 days before or after surgery; group 3, patients who presented positive RT-PCR > 10 days after surgery. The primary outcome was mortality and secondary outcomes were postoperative complications, intensive care unit (ICU) length of stay, and postoperative days of hospitalization. RESULTS: The three groups were similar with respect to age, the European System of Cardiac Operative Risk Evaluation score, and comorbidities, except hypertension. Postoperative complications and death were significantly higher in groups 2 and 3 than in group 1, and no significant difference between groups 2 and 3 was seen. Group 2 showed a high prevalence of surgery performed as an urgent procedure. Although no significant differences were observed in ICU length of stay, total postoperative hospitalization time was significantly higher in group 3 than in groups 1 and 2. CONCLUSION: COVID-19 affecting the postoperative period of patients who underwent cardiovascular surgery is associated with a higher rate of morbidity and mortality. Delaying procedures in RT-PCR-positive patients may help reduce risks of perioperative complications and death.

COVID-19 in the perioperative period of cardiovascular surgery: the brazilian experience

Abstract Introduction: We investigated the clinical course and outcomes of patients submitted to cardiovascular surgery in Brazil and who had developed symptoms/signs of coronavirus disease 2019 (COVID-19) in the perioperative period. Methods: A retrospective multicenter study including 104 patients who were allocated in three groups according to time of positive real time reverse transcriptase-polymerase chain reaction (RT-PCR) for the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2): group 1, patients who underwent cardiac surgery > 10 days after positive RT-PCR; group 2, patients with a positive RT-PCR within 10 days before or after surgery; group 3, patients who presented positive RT-PCR > 10 days after surgery. The primary outcome was mortality and secondary outcomes were postoperative complications, intensive care unit (ICU) length of stay, and postoperative days of hospitalization. Results: The three groups were similar with respect to age, the European System of Cardiac Operative Risk Evaluation score, and comorbidities, except hypertension. Postoperative complications and death were significantly higher in groups 2 and 3 than in group 1, and no significant difference between groups 2 and 3 was seen. Group 2 showed a high prevalence of surgery performed as an urgent procedure. Although no significant differences were observed in ICU length of stay, total postoperative hospitalization time was significantly higher in group 3 than in groups 1 and 2. Conclusion: COVID-19 affecting the postoperative period of patients who underwent cardiovascular surgery is associated with a higher rate of morbidity and mortality. Delaying procedures in RT-PCR-positive patients may help reduce risks of perioperative complications and death.

Synthetic enamine naphthoquinone derived from lawsone as cytotoxic agents assessed by in vitro and in silico evaluations.

We synthesized ten enamine naphthoquinones with yields ranging from 43 to 76%. These compounds were screened for their in vitro antiproliferative activities by MTT assay against four types of human cancer cell lines: HCT116, PC3, HL60 and SNB19. The naphthoquinones bearing the picolylamine (7) and quinoline (12) moieties were the most actives (IC50 < 24 µM for all the cell lines), which were comparable or better to the values obtained for the control drugs. In silico evaluations allowed us to develop a qualitative Structure-Activity Relationship which suggest that electrostatic features, particularly the C2-C3 internuclear repulsion and the molecular dipole moment, relate to the biological response. Furthermore, Molecular Docking simulations indicate that the synthetic compounds have the potential to act as anticancer molecules by inhibiting topoisomerase-II and thymidylate synthase.

Synthesis, docking, machine learning and antiproliferative activity of the 6-ferrocene/heterocycle-2-aminopyrimidine and 5-ferrocene-1H-Pyrazole derivatives obtained by microwave-assisted Atwal reaction as potential anticancer agents.

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.

Hydrazones derived from natural aldehydes: in vitro cytotoxic evaluation and in silico pharmacokinetic predictions / Hidrazonas derivadas de aldehídos naturales: evaluación citotóxica in vitro y determinación del perfil farmacocinético in silico / Hidrazonas derivadas de aldeídos naturais: avaliação citotóxica in vitro e determinação de perfil farmacocinético in silico

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.

Immunoconjugates for Cancer Targeting: A Review of Antibody-Drug Conjugates and Antibody-Functionalized Nanoparticles.

Targeted therapy has been recently highlighted due to the reduction of side effects and improvement in overall efficacy and survival from different types of cancers. Considering the approval of many monoclonal antibodies in the last twenty years, cancer treatment can be accomplished by the combination of monoclonal antibodies and small molecule chemotherapeutics. Thus, strategies to combine both drugs in a single administration system are relevant in the clinic. In this context, two strategies are possible and will be further discussed in this review: antibody-drug conjugates (ADCs) and antibody-functionalized nanoparticles. First, it is important to better understand the possible molecular targets for cancer therapy, addressing different antigens that can selectively bind to antibodies. After selecting the best target, ADCs can be prepared by attaching a cytotoxic drug to an antibody able to target a cancer cell antigen. Briefly, an ADC will be formed by a monoclonal antibody (MAb), a cytotoxic molecule (cytotoxin) and a chemical linker. Usually, surface-exposed lysine or the thiol group of cysteine residues are used as anchor sites for linker-drug molecules. Another strategy that should be considered is antibody-functionalized nanoparticles. Basically, liposomes, polymeric and inorganic nanoparticles can be attached to specific antibodies for targeted therapy. Different conjugation strategies can be used, but nanoparticles coupling between maleimide and thiolated antibodies or activation with the addition of ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/ N-hydroxysuccinimide (NHS) (1:5) and further addition of the antibody are some of the most used strategies. Herein, molecular targets and conjugation strategies will be presented and discussed to better understand the in vitro and in vivo applications presented. Also, the clinical development of ADCs and antibody-conjugated nanoparticles are addressed in the clinical development section. Finally, due to the innovation related to the targeted therapy, it is convenient to analyze the impact on patenting and technology. Information related to the temporal evolution of the number of patents, distribution of patent holders and also the number of patents related to cancer types are presented and discussed. Thus, our aim is to provide an overview of the recent developments in immunoconjugates for cancer targeting and highlight the most important aspects for clinical relevance and innovation.

The Effects of the Alkaloid Tambjamine J on Mice Implanted with Sarcoma 180 Tumor Cells.

The tambjamines are a small group of bipyrrolic alkaloids that, collectively, display a significant range of biological activities including antitumor, antimicrobial and immunosuppressive properties. The key objective of the present study was to undertake preclinical assessments of tambjamine J (T-J) so as to determine its in vivo antitumor effects. To that end, sarcoma 180 cells were transplanted in mice and the impacts of the title compound then evaluated using a range of protocols including hematological, biochemical, histopathological, genotoxic and clastogenic assays. As a result it was established that this alkaloid has a significant therapeutic window and effectively reduces tumor growth (by 40 % and 79 % at doses of 10 and 20 mg/kg/day, respectively). In this regard it displays similar antitumor activity to the anticancer agent cyclophosphamide and alters animal weight in an analogous manner.

Naphthoquinone-based Hydrazone Hybrids: Synthesis and Potent Activity Against Cancer Cell Lines.

BACKGROUND: Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, and the modification at their redox center is an interesting strategy to overcome such harmful activity. OBJECTIVE: In this study, four novel semisynthetic hydrazones, derived from the isomers α- and ß- lapachones (α and ß, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity. METHODS: The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media. RESULTS: The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, compounds 3 and 4 being the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than ß-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC50 values in the range 2.90-12.40 µM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte. CONCLUSION: These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.

(Ir)responsabilidade social empresarial: uma avaliação do desastre de Mariana-MG / (Ir)responsabilidad social empresarial: evaluación del desastre de Mariana-MG / Corporate social (ir)responsibility: an analysis of the disaster in Mariana-Brazil

Resumo A temática irresponsabilidade social empresarial (IrSE) ganhou destaque na literatura mundial. No Brasil, o desastre causado pela Samarco Mineração S.A. em 2015 foi alvo de repercussão, constituindo uma oportunidade para estudar a IrSE. O objetivo deste estudo foi investigar se a identificação social com a empresa, que surge em função dos benefícios econômicos, reduz a intenção punitiva e a atribuição de culpa. O instrumento de pesquisa contém escalas com indicadores psicométricos aplicados a 1.616 indivíduos. Constatou-se que os benefícios para a economia local reduziram a intenção punitiva nas cidades de Anchieta-ES, Guarapari-ES e Mariana-MG. O que não ocorreu nas cidades de Colatina-ES e Linhares-ES, que não recebem benefícios econômicos, mas foram afetadas pelo desastre. Identificou-se, ainda, que a severidade do evento aumentou a atribuição de culpa e a intenção punitiva aumentou a intenção de comentários negativos. Como principal conclusão, onde a empresa gerou benefícios, as pessoas estavam menos propensas a puni-la.

Resumen La temática irresponsabilidad social empresarial (IrSE) ganó prominencia en la literatura mundial. En Brasil, el desastre causado por Samarco Mineração S.A. en 2015 fue objeto de repercusión, constituyendo una oportunidad para estudiar la IrSE. El objetivo de este estudio fue investigar si la identificación social con la empresa, que surge en función de los beneficios económicos, reduce la intención punitiva y la atribución de culpa. El instrumento de investigación contiene escalas con indicadores psicométricos aplicados a 1.616 individuos. Se constató que los beneficios para la economía local redujeron la intención punitiva en las ciudades de Anchieta, ES; Guarapari, ES y Mariana, MG. Lo que no ocurrió en las ciudades de Colatina, ES y Linhares-ES, que no reciben beneficios económicos y fueron afectadas por el desastre. Se identificó además que la severidad del acontecimiento aumentó la atribución de culpa y la intención punitiva aumentó la intención de comentarios negativos. Como conclusión, donde la empresa generó beneficios, la gente estaba menos propensa a castigarla.

Abstract The issue of corporate social irresponsibility (CSIR) has gained prominence in world literature. This study analyzes the 2015 environmental disaster caused by Samarco Mineração S.A. in Mariana (MG), Brazil, as an example of CSIR. The objective was to understand whether the population's social identification with the company, which is translated into the economic benefits, reduced punitive intention, and blame attribution. The research instrument uses scales with psychometric indicators applied to 1,616 individuals. It was verified that the benefits to the local economy reduced the punitive intention in the municipalities of Anchieta and Guarapari (ES), and Mariana (MG). This was not the case for Colatina and Linhares (ES). Also, it was observed that the disaster's severity increased blame attribution, and the punitive intention increased the intention to engage in negative word-of-mouth (WOM) about the company. As the main conclusion, people were less likely to punish the company in the municipalities where it generated economic benefits.