Adenylyl cyclase type 9 gene polymorphisms are associated with asthma and allergy in Brazilian children

Barreto, Maurício Lima. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-06T16:05:16Z No. of bitstreams: 1 Teixeira HM Adenylyl cyclase type 9 gene ....pdf: 1921826 bytes, checksum: a47e5fe042de9b5bc2df29ff069a8a29 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-06T16:11:36Z (GMT) No. of bitstreams: 1 Teixeira HM Adenylyl cyclase type 9 gene ....pdf: 1921826 bytes, checksum: a47e5fe042de9b5bc2df29ff069a8a29 (MD5)Made available in DSpace on 2018-04-06T16:11:36Z (GMT). No. of bitstreams: 1 Teixeira HM Adenylyl cyclase type 9 gene ....pdf: 1921826 bytes, checksum: a47e5fe042de9b5bc2df29ff069a8a29 (MD5) Previous issue date: 2017Universidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Saúde Coletiva. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, BrasilAsthma is a chronic inflammatory disease of the respiratory tract. This heterogeneous disease is caused by the interaction of interindividual genetic variability and environmental factors. The gene adenylyl cyclase type 9 (ADCY9) encodes a protein called adenylyl cyclase (AC), responsible for producing the second messenger cyclic AMP (cAMP). cAMP is produced by T regulatory cells and is involved in the down-regulation of T effector cells. Failures in cAMP production may be related to an imbalance in the regulatory immune response, leading to immune-mediated diseases, such as allergic disorders. The aim of this study was to investigate how polymorphisms in the ADCY9 are associated with asthma and allergic markers. The study comprised 1309 subjects from the SCAALA (Social Changes Asthma and Allergy in Latin America) program. Genotyping was accomplished using the Illumina 2.5 Human Omni bead chip. Logistic regression was used to assess the association between allergy markers and ADCY9 variation in PLINK 1.07 software with adjustments for sex, age, helminth infection and ancestry markers. The ADCY9 candidate gene was associated with different phenotypes, such as asthma, specific IgE, skin prick test, and cytokine production. Among 133 markers analyzed, 29 SNPs where associated with asthma and allergic markers in silico analysis revealed the functional impact of the 6 SNPs on ADCY9 expression. It can be concluded that polymorphisms in the ADCY9 gene are significantly associated with asthma and/or allergy markers. We believe that such polymorphisms may lead to increased expression of adenylyl cyclase with a consequent increase in immunoregulatory activity. Therefore, these SNPs may offer an impact on the occurrence of these conditions in admixture population from countries such as Brazil

Correlation between DNA/HSA-interactions and antimalarial activity of acridine derivatives: Proposing a possible mechanism of action

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-02-04T12:52:10Z No. of bitstreams: 1 SILVA, M.M. Correlation between DNA-HSA...2018.pdf: 1799843 bytes, checksum: 61b5a53ca8fb1166e0656deb9687d441 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-02-04T13:08:06Z (GMT) No. of bitstreams: 1 SILVA, M.M. Correlation between DNA-HSA...2018.pdf: 1799843 bytes, checksum: 61b5a53ca8fb1166e0656deb9687d441 (MD5)Made available in DSpace on 2019-02-04T13:08:06Z (GMT). No. of bitstreams: 1 SILVA, M.M. Correlation between DNA-HSA...2018.pdf: 1799843 bytes, checksum: 61b5a53ca8fb1166e0656deb9687d441 (MD5) Previous issue date: 2018Instituto de Química e Biotecnologia (UFAL), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), FAPEAL (Process number 60030 000863/2016), FAPESB, FAPESQ and FACEPE. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Universidade Estadual da Paraíba. Laboratório de Síntese e Vetorização de Moléculas. Departamento de Ciências Biológicas. João Pessoa, PB, Brasil.Universidade Estadual da Paraíba. Laboratório de Síntese e Vetorização de Moléculas. Departamento de Ciências Biológicas. João Pessoa, PB, Brasil.Universidade Estadual da Paraíba. Laboratório de Síntese e Vetorização de Moléculas. Departamento de Ciências Biológicas. João Pessoa, PB, Brasil.Universidade Federal de Pernambuco. Laboratório de Planejamento e Síntese de Fármacos. Departamento de Antibióticos. Recife, PE, Brasil.Universidade Estadual da Paraíba. Laboratório de Síntese e Vetorização de Moléculas. Departamento de Ciências Biológicas. João Pessoa, PB, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil / Universidade Federal de Alagoas. Laboratório de Química Medicinal, Escola de Enfermagem e Farmácia. Macéio, AL, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil / Universidade Federal de Alagoas. Laboratório de Química Medicinal, Escola de Enfermagem e Farmácia. Macéio, AL, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Acridines are considered an important class of compounds due to their wide variety of biological activities. In this work, we synthesized four acridine derivatives (1-4) and evaluated their biological activity against the Plasmodium falciparum W2 line, as well as studied the interaction with ctDNA and HSA using spectroscopic techniques and molecular docking. The acridine derivative 2 (IC50 = 0.90 ± 0.08 μM) was more effective against P. falciparum than primaquine (IC50 = 1.70 ± 0.10 μM) and similar to amsacrine (IC50 = 0.80 ± 0.10 μM). In the fluorescence and UV-vis assays, it was verified that the acridine derivatives interact with ctDNA and HSA leading to a non-fluorescent supramolecular complex formation. The non-covalent binding constants ranged from 2.09 to 7.76 × 103 M-1, indicating moderate interaction with ctDNA. Through experiments with KI, fluorescence contact energy transfer and competition assays were possible to characterize the main non-covalent binding mode of the acridines evaluated with ctDNA as intercalation. The binding constants obtained showed a high linear correlation with the IC50 values against the antimalarial activity, suggesting that DNA may be the main biological target of these molecules. Finally, HSA interaction studies were performed and all evaluated compounds bind to the site II of the protein. The less active compounds (1 and 3) presented the highest affinity to HSA, indicating that the interaction with carrier protein can affect the (bio)availability of these compounds to the biological target