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Percorrer por autor "Carvalho, Eduardo Miguel Da Costa"

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  • Natural products as collagenase inhibitors: a molecular modelling approach
    Publication . Carvalho, Eduardo Miguel Da Costa; Abreu, Rui M.V.; Mateus, Cristiano
    Skin photoaging is a process that involves the degradation of extracellular matrix proteins, including collagen and elastin. These are essential components of the skin, providing sturdiness and elasticity; their degradation leads to the loss of tensile strength, flexibility, and the development of wrinkles. This process is mediated by matrix metalloproteinases (MMPs), including Collagenase (MMP-1). Excessive production of MMP-1 accelerates extrinsic skin ageing, which may be mitigated by applying anti-ageing compounds with anti-collagenase activities. Therefore, there’s interest in discovering better MMP-1 inhibitors, with emphasis on natural compounds, since there’s been a significant shift in market interest towards the usage of natural products in cosmeceutical development. One way to quickly test a wide range of compounds with minimal costs is to rely on in silico methodologies to predict compound bioactivities. This study aimed to explore different molecular modelling approaches to assess the inhibition potential of different natural products against MMP-1, namely molecular docking and quantitative structure-activity relationship (QSAR) modelling. For this purpose, a virtual library of 83 known MMP-1 inhibitors was developed and used to develop QSAR models. QSAR model 2 was selected for further use since it presented solid statistical parameters, with an R² value of 0.96 and a RMSE value of 0.191. A library of natural compounds, with a structure similar to compounds used to develop the QSAR models, was constructed using the COCONUT database of natural compounds. A total of 715 compounds were gathered, and the QSAR model 2 was applied to it. The molecular docking approach was also validated by performing a Re-Docking protocol, and the validated approach was applied in the same library of 715 compounds. Finally, the data from the two methods were combined. Using this data, the tested compounds were ranked according to their combined inhibition probability (%) and the top 10 ranked compounds were analyzed in terms of their structure and binding conformations. In the future, it would be of interest to buy these compounds and test them experimentally to validate these in silico models and confirm the predicted inhibition activity. If this activity is confirmed, then these compounds could be used in cosmeceutical and drug design applications.
    2025Dissertação de mestrado Acesso aberto Ver mais