Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2H)-one as Novel Scaffold for FABP4 Inhibition

Letizia Crocetti; Giuseppe Floresta; Chiara Zagni; Divya Merugu; Francesca Mazzacuva; Renan Rodrigues de Oliveira Silva; Claudia Vergelli; Maria Paola Giovannoni; Agostino Cilibrizzi

doi:10.3390/ph15111335

Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2H)-one as Novel Scaffold for FABP4 Inhibition

Letizia Crocetti, Giuseppe Floresta, Chiara Zagni, Divya Merugu, Francesca Mazzacuva, Renan Rodrigues de Oliveira Silva, Claudia Vergelli, Maria Paola Giovannoni, Agostino Cilibrizzi

Department for Health

Research output: Contribution to journal › Article › peer-review

5 Citations (SciVal)

Abstract

Fatty acid binding protein (FABP4) inhibitors are of synthetic and therapeutic interest and ongoing clinical studies indicate that they may be a promise for the treatment of cancer, as well as other diseases. As part of a broader research effort to develop more effective FABP4 inhibitors, we sought to identify new structures through a two-step computing assisted molecular design based on the established scaffold of a co-crystallized ligand. Novel and potent FABP4 inhibitors have been developed using this approach and herein we report the synthesis, biological evaluation and molecular docking of the 4-amino and 4-ureido pyridazinone-based series.

Original language	English
Article number	1335
Journal	Pharmaceuticals
Volume	15
Issue number	11
Early online date	28 Oct 2022
DOIs	https://doi.org/10.3390/ph15111335
Publication status	Published - 30 Nov 2022

Bibliographical note

Funding Information:
This research has received funding for a scholarship to R.R.d.O.S from the Coordination for the Improvement of Higher Education Personnel—Brazil (CAPES-PRINT, funding number 88887.570120/2020-00).

Keywords

computing assisted molecular design
FABP4
FABP4 inhibitors
FABP4is
fatty acid binding protein
pyridazinone

ASJC Scopus subject areas

Molecular Medicine
Pharmaceutical Science
Drug Discovery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/ph15111335Licence: CC BY

Cite this

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title = "Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2H)-one as Novel Scaffold for FABP4 Inhibition",

abstract = "Fatty acid binding protein (FABP4) inhibitors are of synthetic and therapeutic interest and ongoing clinical studies indicate that they may be a promise for the treatment of cancer, as well as other diseases. As part of a broader research effort to develop more effective FABP4 inhibitors, we sought to identify new structures through a two-step computing assisted molecular design based on the established scaffold of a co-crystallized ligand. Novel and potent FABP4 inhibitors have been developed using this approach and herein we report the synthesis, biological evaluation and molecular docking of the 4-amino and 4-ureido pyridazinone-based series.",

keywords = "computing assisted molecular design, FABP4, FABP4 inhibitors, FABP4is, fatty acid binding protein, pyridazinone",

author = "Letizia Crocetti and Giuseppe Floresta and Chiara Zagni and Divya Merugu and Francesca Mazzacuva and {de Oliveira Silva}, {Renan Rodrigues} and Claudia Vergelli and Giovannoni, {Maria Paola} and Agostino Cilibrizzi",

note = "Funding Information: This research has received funding for a scholarship to R.R.d.O.S from the Coordination for the Improvement of Higher Education Personnel—Brazil (CAPES-PRINT, funding number 88887.570120/2020-00). ",

year = "2022",

month = nov,

day = "30",

doi = "10.3390/ph15111335",

language = "English",

volume = "15",

journal = "Pharmaceuticals",

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T1 - Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2H)-one as Novel Scaffold for FABP4 Inhibition

AU - Crocetti, Letizia

AU - Floresta, Giuseppe

AU - Zagni, Chiara

AU - Merugu, Divya

AU - Mazzacuva, Francesca

AU - de Oliveira Silva, Renan Rodrigues

AU - Vergelli, Claudia

AU - Giovannoni, Maria Paola

AU - Cilibrizzi, Agostino

N1 - Funding Information: This research has received funding for a scholarship to R.R.d.O.S from the Coordination for the Improvement of Higher Education Personnel—Brazil (CAPES-PRINT, funding number 88887.570120/2020-00).

PY - 2022/11/30

Y1 - 2022/11/30

N2 - Fatty acid binding protein (FABP4) inhibitors are of synthetic and therapeutic interest and ongoing clinical studies indicate that they may be a promise for the treatment of cancer, as well as other diseases. As part of a broader research effort to develop more effective FABP4 inhibitors, we sought to identify new structures through a two-step computing assisted molecular design based on the established scaffold of a co-crystallized ligand. Novel and potent FABP4 inhibitors have been developed using this approach and herein we report the synthesis, biological evaluation and molecular docking of the 4-amino and 4-ureido pyridazinone-based series.

AB - Fatty acid binding protein (FABP4) inhibitors are of synthetic and therapeutic interest and ongoing clinical studies indicate that they may be a promise for the treatment of cancer, as well as other diseases. As part of a broader research effort to develop more effective FABP4 inhibitors, we sought to identify new structures through a two-step computing assisted molecular design based on the established scaffold of a co-crystallized ligand. Novel and potent FABP4 inhibitors have been developed using this approach and herein we report the synthesis, biological evaluation and molecular docking of the 4-amino and 4-ureido pyridazinone-based series.

KW - computing assisted molecular design

KW - FABP4

KW - FABP4 inhibitors

KW - FABP4is

KW - fatty acid binding protein

KW - pyridazinone

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U2 - 10.3390/ph15111335

DO - 10.3390/ph15111335

M3 - Article

AN - SCOPUS:85141789524

SN - 1424-8247

VL - 15

JO - Pharmaceuticals

JF - Pharmaceuticals

IS - 11

M1 - 1335

ER -

Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2H)-one as Novel Scaffold for FABP4 Inhibition

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Avance 300 MHz Nuclear Magnetic Resonance (NMR) Spectrometer (1South)

Cite this

Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2H)-one as Novel Scaffold for FABP4 Inhibition

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Equipment

Avance 300 MHz Nuclear Magnetic Resonance (NMR) Spectrometer (1South)

Cite this