PMID- 35744994
OWN - NLM
STAT- MEDLINE
DCOM- 20220627
LR  - 20220716
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 27
IP  - 12
DP  - 2022 Jun 16
TI  - Repositioning of Quinazolinedione-Based Compounds on Soluble Epoxide Hydrolase 
      (sEH) through 3D Structure-Based Pharmacophore Model-Driven Investigation.
LID - 10.3390/molecules27123866 [doi]
LID - 3866
AB  - The development of new bioactive compounds represents one of the main purposes of 
      the drug discovery process. Various tools can be employed to identify new drug 
      candidates against pharmacologically relevant biological targets, and the search 
      for new approaches and methodologies often represents a critical issue. In this 
      context, in silico drug repositioning procedures are required even more in order 
      to re-evaluate compounds that already showed poor biological results against a 
      specific biological target. 3D structure-based pharmacophoric models, usually 
      built for specific targets to accelerate the identification of new promising 
      compounds, can be employed for drug repositioning campaigns as well. In this 
      work, an in-house library of 190 synthesized compounds was re-evaluated using a 
      3D structure-based pharmacophoric model developed on soluble epoxide hydrolase 
      (sEH). Among the analyzed compounds, a small set of quinazolinedione-based 
      molecules, originally selected from a virtual combinatorial library and showing 
      poor results when preliminarily investigated against heat shock protein 90 
      (Hsp90), was successfully repositioned against sEH, accounting the related built 
      3D structure-based pharmacophoric model. The promising results here obtained 
      highlight the reliability of this computational workflow for accelerating the 
      drug discovery/repositioning processes.
FAU - Gazzillo, Erica
AU  - Gazzillo E
AD  - Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 
      Fisciano, SA, Italy.
FAU - Terracciano, Stefania
AU  - Terracciano S
AD  - Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 
      Fisciano, SA, Italy.
FAU - Ruggiero, Dafne
AU  - Ruggiero D
AD  - Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 
      Fisciano, SA, Italy.
FAU - Potenza, Marianna
AU  - Potenza M
AD  - The Italian Foundation for Cancer Research, Institute of Molecular Oncology, Via 
      Adamello 16, 20139 Milan, MI, Italy.
FAU - Chini, Maria Giovanna
AU  - Chini MG
AD  - Department of Biosciences and Territory, University of Molise, C. da Fonte 
      Lappone, 86090 Pesche, IS, Italy.
FAU - Lauro, Gianluigi
AU  - Lauro G
AUID- ORCID: 0000-0001-5065-9717
AD  - Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 
      Fisciano, SA, Italy.
FAU - Fischer, Katrin
AU  - Fischer K
AD  - Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, 
      Friedrich-Schiller-University, Philosophenweg 14, 07743 Jena, Germany.
FAU - Hofstetter, Robert Klaus
AU  - Hofstetter RK
AUID- ORCID: 0000-0002-1077-9703
AD  - Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, 
      Friedrich-Schiller-University, Philosophenweg 14, 07743 Jena, Germany.
FAU - Giordano, Assunta
AU  - Giordano A
AUID- ORCID: 0000-0001-8139-407X
AD  - Institute of Biomolecular Chemistry (ICB), Consiglio Nazionale delle Ricerche 
      (CNR), Via Campi Flegrei 34, 80078 Pozzuoli, NA, Italy.
FAU - Werz, Oliver
AU  - Werz O
AUID- ORCID: 0000-0002-5064-4379
AD  - Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, 
      Friedrich-Schiller-University, Philosophenweg 14, 07743 Jena, Germany.
FAU - Bruno, Ines
AU  - Bruno I
AD  - Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 
      Fisciano, SA, Italy.
FAU - Bifulco, Giuseppe
AU  - Bifulco G
AD  - Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 
      Fisciano, SA, Italy.
LA  - eng
GR  - 21397/Italian Association for Cancer Research/
PT  - Journal Article
DEP - 20220616
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Quinazolinones)
RN  - 0 (Receptors, Drug)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Drug Repositioning
MH  - Enzyme Inhibitors
MH  - *Epoxide Hydrolases/metabolism
MH  - *Quinazolinones
MH  - Receptors, Drug
MH  - Reproducibility of Results
MH  - Solubility
PMC - PMC9228872
OTO - NOTNLM
OT  - anti-inflammatory agents
OT  - chemical synthesis
OT  - computational techniques
OT  - drug discovery
OT  - drug repositioning
OT  - soluble epoxide hydrolase
COIS- The authors declare that they have no conflict of interest.
EDAT- 2022/06/25 06:00
MHDA- 2022/06/28 06:00
PMCR- 2022/06/16
CRDT- 2022/06/24 01:33
PHST- 2022/05/09 00:00 [received]
PHST- 2022/06/08 00:00 [revised]
PHST- 2022/06/14 00:00 [accepted]
PHST- 2022/06/24 01:33 [entrez]
PHST- 2022/06/25 06:00 [pubmed]
PHST- 2022/06/28 06:00 [medline]
PHST- 2022/06/16 00:00 [pmc-release]
AID - molecules27123866 [pii]
AID - molecules-27-03866 [pii]
AID - 10.3390/molecules27123866 [doi]
PST - epublish
SO  - Molecules. 2022 Jun 16;27(12):3866. doi: 10.3390/molecules27123866.