Background: Leishmaniosis is a neglected tropical disease and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a key enzyme in the design of new drugs to fight this disease. Objective: The present study aimed to evaluate potential inhibitors of GAPDH enzyme found in Leishmania mexicana (L. mexicana). Method: A search for novel antileishmanial molecules was carried out based on similarities from pharmacophoric points related to the binding site of the crystallographic enzyme using the ZINCPharmer server. The molecules selected in this screening were subjected to molecular docking and molecular dynamics simulations. Results: Consensual analysis of the docking energy values was performed, resulting in the selection of ten compounds. These ligand-receptor complexes were visually inspected in order to analyze the main interactions and subjected to toxicophoric evaluation, culminating in the selection of three compounds, which were subsequently submitted to molecular dynamics simulations. The docking results showed that the selected compounds interacted with GAPDH from L. mexicana, especially by hydrogen bonds with Cys166, Arg249, His194, Thr167, and Thr226. From the results obtained from molecular dynamics, it was observed that one of the loop regions, corresponding to the residues 195-222, can be related to the fitting of the substrate at the binding site, assisting in the positioning and the molecular recognition via residues responsible for the catalytic activity. Conclusion: The use of molecular modeling techniques enabled the identification of promising compounds as inhibitors of the GAPDH enzyme from L. mexicana, and the results obtained here can serve as a starting point to design new and more effective compounds than those currently available.
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Introduction: Type C hepatitis, an infectious disease considered a global health problem, presents risks for congenital malformation, low weight and higher rates of perinatal mortality, and its condition may induce an increase in the maternal mortality rate. Objective: Verify epidemiological aspects of type C Hepatitis in pregnant women in city of Belém of state of Pará. Methodology: It is a descriptive research with information from DATASUS-SINAN database, which seven filters were used to obtain the epidemiological data of pregnant women, aged between 10 to 59 years old, in the period from January of 2008 to December of 2018, with laboratory confirmation for type C virus, anti-HCV reagent serology. Results: 510 cases of pregnant women with type C hepatitis were reported, with anti-HCV serology confirmation, noting that the second trimester of pregnancy had showed the highest absolute number with 12 cases (2.35%) of infected pregnant women, followed by the third trimester with 07 cases (1.37%) and the first trimester with 05 cases (0.98%), respectively. It was found that 17 cases (3.33%) did not correspond to any of the gestational periods, being ignored or in the "blank" section of the database. Most pregnant women (70.83%) comprised the age group of 20 to 39 years old; 6.9% represent cases of inconclusive fulminant hepatitis; 3.13% acute type C hepatitis and 88.82% chronic type C hepatitis; whose main route of contamination was sexual (5.68%). Conclusion: Therefore, type C hepatitis occurs mainly between the second and third trimesters, with sexual and injectable transmission, which reinforces the importance of a wellperformed prenatal care, allowing for early measures to be taken.
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