Browsing by Author "Marques, Filipe Mendanha"
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- Study of the anti-diabetic potential of a Fungi Marine Compounds library by virtual screening against 11β- HSD1Publication . Marques, Filipe Mendanha; Abreu, Rui M.V.; Shiraishi, CarlosType 2 diabetes mellitus (DM) is a chronic metabolic disease whose prevalence has been steadily increasing worldwide. Type 2 DM (formerly known as non-insulin-dependent DM) is the most common form of DM, characterized by hyperglycemia, insulin resistance, and relative insulin deficiency. This metabolic disease results from the interaction between genetic, environmental and behavioral risk factors. One of the proteins involved in this disease is 11β-hydroxysteroid dehydrogenase type 1 (11β- HSD1), an enzyme responsible for the reduction of cortisone to its active form, cortisol, which can lead to metabolic alterations such as insulin resistance and hyperglycemia. Thus, inhibition of 11β-HSD1 may offer a novel therapeutic approach for type 2 diabetes mellitus. Marine fungi (MF) compounds have been the subject of great attention in drug discovery because of their promise as therapeutic agents and because they possess a range of activities, including antibacterial, antiviral, and anticancer agents. This study prepared a virtual library of 157 compounds in marine fungi (MF). The potential of the compounds in the MF library as inhibitors of the 11β-HSD1 was then evaluated. Molecular docking of the MF library was performed against the 3D structure of 11β-HSD1 using VINA and YASARA software. Out of the 157 compounds, the 3 compounds that presented lower predicted binding energies (ΔG) values were Brevione A, Brevione I and Ilicicolin H with ΔG values of -11.6, -11.4 and -10.9 (kcal/mol), respectively. Brevione A and Brevione I are present in marine fungi Penicillium sp, while Ilicicolin H is present in Campylocarpon sp. HDN13-308. A detailed analysis of the predicted binding conformation of the 3 compounds was performed, and the main residues involved in the predicted binding conformation were analyzed in detail. Although experimental validation is needed, the 3 highlighted compounds, especially Brevione I, can be considered promising leads for developing potential anti-diabetic therapeutics. Also, the MF library prepared will be made available for researchers in general and will eventually be used to virtually screen other protein targets of interest.