Browsing by Author "Coelho, Luiz Felipe Leomil"

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    Benzophenone derivatives showed dual anti-inflammatory and antiproliferative activities by inhibiting cox enzymes and promote cyclin e downregulation.
    (2022) Folquitto, Laís Regina dos Santos; Souza, Thiago Belarmino de; Januário, Jaqueline Pereira; Nascimento, Isadora M.; Brandão, Brenda Tavares de Vasconcelos; Moreira, Maria E. C.; Horvath, Renato de Oliveira; Santos, Marcelo Henrique dos; Coelho, Luiz Felipe Leomil; Veloso, Marcia Paranho; Soares, Marisi Gomes; Carvalho, Diogo Teixeira; Ionta, Marisa; Paula, Daniela Aparecida Chagas de; Dias, Danielle Ferreira
    Considering the promising antitumor effects of compounds with dual anti-inflammatory and antiproliferative activities, thus benzophenones analogs (2-7) were evaluated on in vivo anti- inflammatory assay and molecular docking analysis. Those with the best molecular docking results were in vitro evaluated on cyclooxygenase (COX) enzymes and tested regarding antiproliferative activity. All derivatives displayed in vivo anti-inflammatory activity. Among them, the substances 2’-hydroxy-4’-benzoylphenyl-β-D-glucopyranoside (4), 4-hydroxy-4’-methoxybenzophenone (5) and 4’-(4’’-methoxybenzoyl)phenyl-β-D-glucopyranoside (7)showed the best values of Glide Score in COX-2 docking evaluation and 4 and 5 selectively inhibited COX-2 and COX-1 in vitro enzymatic assay, respectively. Thus, 4 and 5 were tested against breast cancer (MCF-7, MDA-MB-231, Hs578T) and non-small-cell-lung cancer (A549) cell lines. The estrogen-positive MCF-7 cell line was more responsive compared to other tested cell lines. They induced cell cycle arrest at G1/S transition in MCF-7 cell line once there was an increase in G0/G1 population with concomitant reduction of S population. The antiproliferative activity of these substances on MCF-7 was associated with their ability to inhibit cyclin E expression, a critical regulator of G1/S transition. Taken together, the data indicate that 4 and 5 have dual anti-inflammatory and antiproliferative activities and support further studies to evaluate their antitumor potential.
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    High prevalence of dengue antibodies and the arginine variant of the FcγRIIa polymorphism in asymptomatic individuals in a population of Minas Gerais State, Southeast Brazil.
    (2017) Pereira, Anna Carolina Toledo da Cunha; Siqueira, Tatiane Ribeiro de; Prado, Andressa Anunciação de Oliveira; Silva, Camila Almeida Veiga da; Moraes, Thaís de Fátima Silva; Aleixo, Alan Alex; Magalhães, José Carlos de; Souza, Gabriel Augusto Pires de; Drumond, Betânia Paiva; Ferreira, Gustavo Portela; Silva, Breno de Mello; Magalhães, Cíntia Lopes de Brito; Santos, Luciana Lara; Ferreira, Jaqueline Maria Siqueira; Malaquias, Luiz Cosme Cotta; Coelho, Luiz Felipe Leomil
    Dengue is the most prevalent arthropod-borne viral illness in humans worldwide. Single-nucleotide polymorphisms (SNPs) in genes involved in the immune response, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), IgG Fc receptor II-A (FcγRIIa), vitamin D receptor (VDR), and tumor necrosis factor alpha (TNF-α), were previously reported to be associated with susceptibility to dengue disease in different human populations. Therefore, due to the relevant association of host immune and genetic status with disease susceptibility/severity of dengue, this work aims to verify the frequency of anti-dengue virus antibodies and some dengue-associated risk SNPs in a population in Minas Gerais State, Southeast Brazil. A total of 1560 individuals were genotyped for polymorphisms in DC-SIGN (rs4804803), FcγRIIa (rs1801274), VDR (rs7975232), and TNF-α (rs1800629). The presence of anti-dengue antibodies (IgM and/or IgG) in these samples was also assayed. Anti-dengue antibodies were detected at an overall frequency of 16.86%, indicating a virus infection in asymptomatic individuals. The genotypic frequencies of all SNPs studied did not differ between the asymptomatic and control groups. Regarding the allelic frequencies of the four SNPs analyzed, a higher frequency was detected of the G allele of FcγRIIa/rs1801274 in the asymptomatic individuals when compared to that in the control group (p =0.03). Therefore, the results showed a high prevalence of asymptomatic individuals in Minas Gerais State, with a potential association between the presence of the G allele of FcγRIIa/rs1801274 and protection against symptomatic disease.
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    Nanoparticles as vaccines to prevent arbovirus infection : a long road ahead.
    (2021) Souza, Gabriel Augusto Pires de; Rocha, Raíssa Prado; Gonçalves, Ricardo Lemes; Ferreira, Cyntia Silva; Silva, Breno de Mello; Castro, Renato Fróes Goulart de; Rodrigues, João Francisco Vitório; Vieira Júnior, João Carlos Vilela; Malaquias, Luiz Cosme Cotta; Abrahão, Jônatas Santos; Coelho, Luiz Felipe Leomil
    Arthropod-borne viruses (arboviruses) are a significant public health problem worldwide. Vaccination is considered one of the most effective ways to control arbovirus diseases in the human population. Nanoparticles have been widely explored as new vaccine platforms. Although nanoparticles’ potential to act as new vaccines against infectious diseases has been identified, nanotechnology’s impact on developing new vaccines to prevent arboviruses is unclear. Thus, we used a comprehensive bibliographic survey to integrate data concerning the use of diverse nanoparticles as vaccines against medically important arboviruses. Our analysis showed that considerable research had been conducted to develop and evaluate nanovaccines against Chikungunya virus, Dengue virus, Zika virus, Japanese encephalitis virus, and West Nile virus. The main findings indicate that nanoparticles have great potential for use as a new vaccine system against arboviruses. Most of the studies showed an increase in neutralizing antibody production after mouse immunization. Nevertheless, even with significant advances in this field, further efforts are necessary to address the nanoparticles’ potential to act as a vaccine against these arboviruses. To promote advances in the field, we proposed a roadmap to help researchers better characterize and evaluate nanovaccines against medically important arboviruses.
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    No effect of prior Dengue virus 1 infection in mouse dams on long-term behavioral profiles in offspring infected with Zika virus during gestation.
    (2020) Costa, Karla Cristinne Mancini; Brancaglion, Gustavo Andrade; Almeida, Carolina Aparecida de Faria; Amorim, Gabriel Estevam Santos de; Veloso, Luciana Lopes; Lião, Lucas da Silva; Souza, Gabriel Augusto Pires de; Pereira, Bruna Pinheiro; Angelo, Marilene Lopes; Ruginsk, Silvia Graciela; Brandão, Wesley Nogueira; Marcourakis, Tania; Ceron, Carla Speroni; Coelho, Luiz Felipe Leomil; Torres, Larissa Helena
    Zika virus (ZIKV) is a mosquito-borne Flavivirus structurally and antigenically related to Dengue virus (DENV). Zika virus has been associated with congenital anomalies and most ZIKV outbreaks have occurred in endemic areas of DENV. The present study investigated the effects of prior DENV serotype 1 (DENV1) immunity in immunocompetent female Swiss mice on gestational ZIKV infection in offspring. Physical/reflex development, locomotor activity, anxiety, visual acuity, and brain-derived neurotrophic factor (BDNF) levels were evaluated in offspring during infancy and adolescence. Anti-DENV1 and anti-ZIKV antibodies were detected in sera of the progenitors, whereas no ZIKV genomes were detected in the offspring brain. Pups from dams with only DENV1 immunity presented alterations of physical/reflex development. Pups from all infected dams exhibited time- related impairments in locomotor activity and anxiolytic-like behavior. Offspring from DENV/ZIKV-infected dams exhibited impairments in visual acuity during infancy but not during adolescence, which was consistent with morphometric analysis of the optic nerve. Pups from DENV1-, ZIKV-, and DENV/ZIKV-infected dams exhibited a decrease in BDNF levels during infancy and an increase during adolescence in distinct brain regions. In summary, we found no influence of prior DENV1 immunity on gestational ZIKV infection in offspring, with the exception of alterations of early visual parameters, and an increase in BDNF levels in the hippocampus during adolescence.
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    SARS-CoV-2 mutations and where to find them : an in silico perspective of structural changes and antigenicity of the spike protein.
    (2020) Gonçalves, Ricardo Lemes; Leite, Túlio César Rodrigues; Dias, Bruna de Paula; Caetano, Camila Carla da Silva; Souza, Ana Clara Gomes de; Batista, Ubiratan da Silva; Barbosa, Camila Cavadas; Reyes Sandoval, Arturo; Coelho, Luiz Felipe Leomil; Silva, Breno de Mello
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    Study of the role of the membrane protein caveolin-1 on Zika virus replication inside THP-1 cells.
    (2019) Rojas Coronel, Alejandra Carla; Silva, Breno de Mello; Silva, Breno de Mello; Coelho, Luiz Felipe Leomil; Almeida, Roberto Farina de
    Zika virus (ZIKV) is an arthropod-borne Flavivirus that affect millions of people worldwide. Its genome is composed of a single-stranded positive RNA that encodes 10 known proteins. It can be transmitted by mosquitos of the Aedes genus, as well as by sexual intercourse and blood transfusion. Although the symptoms of acute ZIKV infection are usually mild and self-limited, it causes microcephaly in fetuses of pregnant women, and Guillian–Barré syndrome in adults. Since no treatment or vaccine has been developed until today, further studies are needed to characterize the interaction between ZIKV proteins and host cells. Recent studies have shown that lipid rafts are known to be preferred sites for interaction between viruses and host cells, which may trigger molecular signaling to favor virus multiplication. Caveolae lipid rafts are a subset of membrane rafts, which molecular marker is caveolin-1 protein, since is the responsible for caveolae formation. They are cellular domains that concentrate plasma membrane proteins and lipids involved in the regulation of cell function, which serve as an organizing center for biological phenomena and cellular signaling. Caveolae lipid rafts involvement in ZIKV processing, replication, and assembly remains poorly characterized. Here, we hypothesized a potential implication of caveolin-1 protein in the replication process for ZIKV inside the cell. This was evaluated by measuring the effect of ZIKV infection on cav-1 expression. Then, it was also studied the effect of lipid raft removal with β-methyl cyclodextrin (β-MCD) and both silencing and overexpression of cav-1, on viral multiplication, using qrt-PCR to detect ZIKV mRNA load on the cell. A decreased of cav-1 expression was observed after infection, suggesting a possible virus modulating role. Furthermore, when cellular cholesterol was depleted by β-MCD treatment after ZIKV entrance, lipid rafts were disrupted and virus genome copies were reduced inside the cell. Additionally, neither cav-1 silencing nor overexpression showed any consistent effect on ZIKV replication. These data suggest an important role of caveolar cholesterol-rich lipid raft microdomains in ZIKV replication, nevertheless further studies need to be made to confirm a specific effect of cav-1 over ZIKV multiplication.
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    Synthesis, activity, and docking studies of eugenol-based glucosides as new agents against Candida sp.
    (2018) Hipolito, Taciane Maira Magalhães; Bastos, Guilherme Tadeu Lemos; Barbosa, Thulio Wliandon Lemos; Souza, Thiago Belarmino de; Coelho, Luiz Felipe Leomil; Dias, Amanda Latercia Tranches; Rodríguez, Ihosvany Camps; Santos, Marcelo Henrique dos; Dias, Danielle Ferreira; Franco, Lucas Lopardi; Carvalho, Diogo Teixeira
    Seventeen new synthetic derivatives of eugenol (6, 8–15 and 8′‐15′) were planned following literature reports on antifungal activities of nitroeugenol and eugenol glucoside. The anti‐Candida activity of these compounds was investigated by in vitro assay, and the cytotoxicity evaluation was performed with the most active compounds. The peracetylated glucosides presented better biological results than their hydroxylated analogues. The glucoside 11, a 4‐nitrobenzamide, showed the best potency (MIC50 range 11.0–151.84 μm), the wider spectrum of action, and overall the best selectivity indexes, especially against C. tropicalis (~30) and C. krusei (~15). To investigate its possible mechanism of action, glucoside 11 was subjected to molecular docking studies with Candida sp. enzymes involved in ergosterol biosynthesis. Results have shown that the peracetyl glucosyl moiety and the 4‐nitrobenzamide group in 11 are effectively involved in its high affinity with the active site of squalene epoxidase.