Fourfold Filtered Statistical/Computational Approach for the Identification of Imidazole Compounds as HO-1 Inhibitors from Natural Products.
Mar Drugs
; 17(2)2019 Feb 12.
Article
em En
| MEDLINE
| ID: mdl-30759842
ABSTRACT
Over-regulation of Heme oxygenase 1 (HO-1) has been recently identified in many types of human cancer, and in these cases, poor clinical outcomes are normally reported. Indeed, the inhibition of HO-1 is being considered as an anticancer approach. Imidazole scaffold is normally present in most of the classical HO-1 inhibitors and seems indispensable to the inhibitory activity due to its strong interaction with the Fe(II) of the heme group. In this paper, we searched for new potentially HO-1 inhibitors among three different databases Marine Natural Products (MNP), ZINC Natural Products (ZNP) and Super Natural II (SN2). 484,527 compounds were retrieved from the databases and filtered through four statistical/computational filters (2D descriptors, 2D-QSAR pharmacophoric model, 3D-QSAR pharmacophoric model, and docking). Different imidazole-based compounds were suggested by our methodology to be potentially active in inhibiting the HO-1, and the results have been rationalized by the bioactivity of the filtered molecules reported in the literature.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
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Inibidores Enzimáticos
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Heme Oxigenase-1
/
Imidazóis
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article