Structure-based design and evaluation of novel N-phenyl-1H-indol-2-amine derivatives for fat mass and obesity-associated (FTO) protein inhibition - Publication - Bridge of Knowledge

Your account

login

Search

Structure-based design and evaluation of novel N-phenyl-1H-indol-2-amine derivatives for fat mass and obesity-associated (FTO) protein inhibition

Abstract

Fat mass and obesity-associated (FTO) protein contributes to non-syndromic human obesity which refers to excessive fat accumulation in human body and results in health risk. FTO protein has become a promising target for anti-obesity medicines as there is an immense need for the rational design of potent inhibitors to treat obesity. In our study, a new scaffold N-phenyl-1H-indol-2-amine was selected as a base for FTO protein inhibitors by applying scaffold hopping approach. Using this novel scaffold, different derivatives were designed by extending scaffold structure with potential functional groups. Molecular docking simulations were carried out by using two different docking algorithm implemented in CDOCKER (flexible docking) and AutoDock programs (rigid docking). Analyzing results of rigid and flexible docking, compound MU06 was selected based on different properties and predicted binding affinities for further analysis. Molecular dynamics simulation of FTO/MU06 complex was performed to characterize structure rationale and binding stability. Certainly, Arg96 and His231 residue of FTO protein showed stable interaction with inhibitor MU06 throughout the production dynamics phase. Three residues of FTO protein (Arg96, Asp233, and His231) were found common in making H-bond interactions with MU06 during molecular dynamics simulation and CDOCKER docking.

Citations

  • 2 5

    CrossRef

  • 0

    Web of Science

  • 2 5

    Scopus

Authors (2)

Cite as

Full text

full text is not available in portal

Keywords

Details

Category:
Articles
Type:
artykuł w czasopiśmie wyróżnionym w JCR
Published in:
COMPUTATIONAL BIOLOGY AND CHEMISTRY no. 64, pages 414 - 425,
ISSN: 1476-9271
Language:
English
Publication year:
2016
Bibliographic description:
Padariya M., Kalathiya U.: Structure-based design and evaluation of novel N-phenyl-1H-indol-2-amine derivatives for fat mass and obesity-associated (FTO) protein inhibition// COMPUTATIONAL BIOLOGY AND CHEMISTRY. -Vol. 64, (2016), s.414-425
DOI:
Digital Object Identifier (open in new tab) 10.1016/j.compbiolchem.2016.09.008
Verified by:
Gdańsk University of Technology

seen 147 times

Recommended for you

Identification of 1H‐indene‐(1, 3, 5, 6)‐tetrol derivatives as potent pancreatic lipase inhibitors using molecular docking and molecular dynamics approach

2016

Molecular basis and potential activity of HIV-1 reverse transcriptase toward trimethylamine-based compounds

2017

Geometry optimization of steroid sulfatase inhibitors - the influence on the free binding energy with STS

2017

Extracting functional groups of ALLINI to design derivatives of FDA‐approved drugs: Inhibition of HIV‐1 integrase

2018
Meta Tags