Due to increasing interest in the field of heme oxygenases (HOs), we built a ligand database called HemeOxDB that includes the entire set of known HO-1 and HO-2 inhibitors, resulting in more than 400 compounds. The HemeOxDB is available online at http://www.researchdsf.unict.it/hemeoxdb/, and having a robust search engine allows end users to build complex queries, sort tabulated results, and generate color-coded two- and three-dimensional graphs. This database will grow to be a tool for the design of potent and selective HO-1 or HO-2 inhibitors. We were also interested in virtually searching for alternative inhibitors, and, for the first time in the field of HOs, a quantitative structure–activity relationship (QSAR) model was built using half-maximal inhibitory concentration (IC50) values of the whole set of known HO-1 inhibitors, taken from the HemeOxDB and employing the Monte Carlo technique. The statistical quality suggested that the model is robust and possesses desirable predictive potential. The screening of US Food and Drug Administration (FDA)-approved drugs, external to our dataset, suggested new predicted inhibitors, opening the way for replacing imidazole groups. The HemeOxDB and the QSAR model reported herein may help in prospectively identifying or repurposing new drugs with optimal structural attributes for HO enzyme inhibition.

Heme Oxygenase Database (HemeOxDB) and QSAR Analysis of Isoform 1 Inhibitors

Amata Emanuele
;
Marrazzo Agostino;Dichiara Maria;Modica Maria;Salerno Loredana;Prezzavento Orazio;Nastasi Giovanni;Rescifina Antonio;Romeo Giuseppe;Pittalà Valeria
2017

Abstract

Due to increasing interest in the field of heme oxygenases (HOs), we built a ligand database called HemeOxDB that includes the entire set of known HO-1 and HO-2 inhibitors, resulting in more than 400 compounds. The HemeOxDB is available online at http://www.researchdsf.unict.it/hemeoxdb/, and having a robust search engine allows end users to build complex queries, sort tabulated results, and generate color-coded two- and three-dimensional graphs. This database will grow to be a tool for the design of potent and selective HO-1 or HO-2 inhibitors. We were also interested in virtually searching for alternative inhibitors, and, for the first time in the field of HOs, a quantitative structure–activity relationship (QSAR) model was built using half-maximal inhibitory concentration (IC50) values of the whole set of known HO-1 inhibitors, taken from the HemeOxDB and employing the Monte Carlo technique. The statistical quality suggested that the model is robust and possesses desirable predictive potential. The screening of US Food and Drug Administration (FDA)-approved drugs, external to our dataset, suggested new predicted inhibitors, opening the way for replacing imidazole groups. The HemeOxDB and the QSAR model reported herein may help in prospectively identifying or repurposing new drugs with optimal structural attributes for HO enzyme inhibition.
heme oxygenase; HemeOxDB; online inhibitor database; QSAR; virtual screening; Databases, Protein; Dose-Response Relationship, Drug; Enzyme Inhibitors; Heme Oxygenase (Decyclizing); Humans; Isoenzymes; Molecular Structure; Quantitative Structure-Activity Relationship; Molecular Medicine; Pharmacology, Toxicology and Pharmaceutics (all); Organic Chemistry
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/314966
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 30
  • ???jsp.display-item.citation.isi??? 29
social impact