Proteases have received enormous interest from the research and medical communities because of their significant roles in several human diseases. Some examples include the involvement of thrombin in thrombosis, HIV-1 protease in Acquired Immune Deficiency Syndrome, cruzain in Trypanosoma cruzi infection, and membrane-type 1 matrix metalloproteinase in tumor invasion and metastasis. Many efforts has been undertaken to design effective inhibitors featuring potent inhibitory activity, specificity, and metabolic stability to those proteases involved in such pathologies. Protease inhibitors usually target the active site, but some of them act by other inhibitory mechanisms. The understanding of the structure-function relationships of proteases and inhibitors has an impact on new inhibitor drugs designing. In this paper, the structures of four proteases (thrombin, HIV-protease, cruzain, and a matrix metalloproteinase) are briefly reviewed, and used as examples of the importance of proteases for the development of new treatment strategies, leading to a longer and healthier life.

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Prostaciclina I 2 inibe a agregação plaquetária pela interação com um receptor específico de membrana. Neste trabalho, desenvolvemos modelos de QSAR-3D para uma série de compostos heterocíclicos aromáticos usando como descritor o volume de interseção local. Os modelos obtidos podem ser aplicados no desenvolvimento de novos ligantes de receptor da PGI 2 com potencial atividade anti-agregante plaquetária.Prostacyclin I 2 inhibits platelet aggregation through specific binding to its membrane receptor. In this work, we developed 3D-QSAR models for a series of aromatic heterocyclic compounds from literature using the local intersection volume descriptor. The models obtained can be applied to design new PGI 2 receptor ligands with potential platelet anti-aggregating activity. Keywords: 3D-QSAR, local intersection volume (LIV), prostacyclin receptor, platelet aggregation IntroductionProstacyclin I 2 (PGI 2 ) (Figure 1) is an endogenous chemical mediator acting as a potent inhibitor of platelet aggregation, interacting with its specific receptor (IP) located on cellular membranes. [1][2][3] Under physiological conditions, prostacyclin is a labile compound of limited clinical usage, 3 which has a half-life of approximately 3 minutes. In order to develop antithrombotic agents with better pharmacokinetic profile, Meanwell and co-workers [4][5][6][7][8] synthesized and evaluated a series of aromatic heterocyclic compounds (see compound 2 in Figure 1). [4][5][6][7][8] Based on data from their research, we developed, in this work, 3D-QSAR models for ligands of IP receptor using the local intersection volume (LIV) descriptor, 9 i.e., the intersection volume between the volumes of the compound atoms and the volumes of a set of spheres of defined atom size. It composes a three-dimensional box, in analogy to the Grid method.10 The LIV-3D-QSAR models were obtained and evaluated by genetic algorithms (GA) and partial least squares (PLS) methods. [11][12][13] They can be applied to design new PGI 2 receptor ligands that could be potential inhibitors of blood platelet aggregation. Methods Steps on the LIV-3D-QSAR models developmentStep 1. Selection of 42 aromatic heterocyclic compounds 4-8 (see Table 1, Supplementary Material) divided in a training data set (30 compounds) and a test data set (12 compounds). The corresponding values of the biological activity 4-8 according to the pharmacological protocol established by Seiler and co-workers 14 are shown on Table 1.Step 2. Construction of a grid matrix composed by cubic unitary cells, where the vertices of the cells 4-8 and pharmacophoric sites (S1, S2, S3, and S4) definition according SAR studies. 5,20 817 Local Intersection Volume (LIV) Descriptors: 3D-QSAR Models Vol. 13, No. 6, 2002 correspond to the Cartesian coordinates of the eight carbon atoms. The vertices arrest lengths are 1.50Å (that is, almost equal to the carbon van der Waals radii of 1.54Å). The grid matrix is composed by a total of 2197 (13x13x13) carbon atoms, constructed on an Excel ® program, and imported into the...

A Pandemia da COVID-19, decreta em março de 2020 pela Organização Mundial de Saúde (OMS), causou grandes impactos econômicos, educacionais, sanitários, sociais, políticos, financeiros e crises na saúde, fundamentado pela recomendação de distanciamento social. Neste sentido muitas escolas e instituições de ensino superior precisaram interromper as atividades presenciais. Os órgãos governamentais precisaram oferecer uma educação segura e longe de riscos da contaminação do coronavírus, através de uma educação remota, usando as Tecnologias Digitais de Informação e Comunicação (TDICs). O presente trabalho visa proporcionar e avaliar experimentos no Ensino de Ciências utilizando materiais alternativos de baixo custo através do novo método de educação, o Ensino Remoto Emergencial (ERE). Foram aplicados os experimentos, as questões relativas às atividades da prática e um questionário (pós-teste) para alunos e professores. Observamos que a maioria dos alunos realizaram os experimentos com sucesso, aumentando seus interesses pela Ciência. Os professores observaram a possibilidade de realizar experimentos através da ERE e o seu impacto na melhoria do processo de ensino-aprendizagem de seus alunos.