Fourfold Filtered Statistical/Computational Approach for the Identification of Imidazole Compounds As HO-1 Inhibitors from Natural Products

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2019 Feb 15

PMID 30759842

Citations 15

Authors

Giuseppe Floresta

Emanuele Amata

Davide Gentile

Giuseppe Romeo

Agostino Marrazzo

Valeria Pittala

Loredana Salerno

Antonio Rescifina

Affiliations

Soon will be listed here.

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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