Evaluation of in vitro aldose redutase inhibitory activity of 5-arylidene-2,4-thiazolidinediones

Rosanna Maccari; Rosaria Ottanà; Rosella Ciurleo; Maria Gabriella Vigorita; Dietmar Rakowitz; Theodora Steindl; Thierry Langer

doi:10.1016/j.bmcl.2007.04.109

Evaluation of in vitro aldose redutase inhibitory activity of 5-arylidene-2,4-thiazolidinediones

Rosanna Maccari, Rosaria Ottanà, Rosella Ciurleo, Maria Gabriella Vigorita, Dietmar Rakowitz, Theodora Steindl, Thierry Langer

IRCCS Centro Neurolesi "Bonino Pulejo"

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

Abstract

A number of 5-arylidene-2,4-thiazolidinediones containing a hydroxy or a carboxymethoxy group in their 5-benzylidene moiety have been synthesised and evaluated as in vitro aldose reductase (ALR2) inhibitors. Most of them exhibited strong inhibitory activity, with IC₅₀ values in the range between 0.20 and 0.70 μM. Molecular docking simulations into the ALR2 active site highlighted that the phenolic or carboxylic substituents of the 5-benzylidene moiety can favourably interact, in alternative poses, either with amino acid residues lining the lipophilic pocket of the enzyme, such as Leu300, or with the positively charged recognition region of the ALR2 active site.

Original language	English
Pages (from-to)	3886-3893
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2007.04.109
Publication status	Published - Jul 15 2007

Keywords

2,4-Thiazolidinediones
Aldose reductase
Diabetes mellitus
Molecular docking

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Organic Chemistry
Drug Discovery
Pharmaceutical Science

Access to Document

10.1016/j.bmcl.2007.04.109

Cite this

@article{d482cc372e8b4fde91b6d0aca236fd04,

title = "Evaluation of in vitro aldose redutase inhibitory activity of 5-arylidene-2,4-thiazolidinediones",

abstract = "A number of 5-arylidene-2,4-thiazolidinediones containing a hydroxy or a carboxymethoxy group in their 5-benzylidene moiety have been synthesised and evaluated as in vitro aldose reductase (ALR2) inhibitors. Most of them exhibited strong inhibitory activity, with IC50 values in the range between 0.20 and 0.70 μM. Molecular docking simulations into the ALR2 active site highlighted that the phenolic or carboxylic substituents of the 5-benzylidene moiety can favourably interact, in alternative poses, either with amino acid residues lining the lipophilic pocket of the enzyme, such as Leu300, or with the positively charged recognition region of the ALR2 active site.",

keywords = "2,4-Thiazolidinediones, Aldose reductase, Diabetes mellitus, Molecular docking",

author = "Rosanna Maccari and Rosaria Ottan{\`a} and Rosella Ciurleo and Vigorita, {Maria Gabriella} and Dietmar Rakowitz and Theodora Steindl and Thierry Langer",

year = "2007",

month = jul,

day = "15",

doi = "10.1016/j.bmcl.2007.04.109",

language = "English",

volume = "17",

pages = "3886--3893",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "14",

}

TY - JOUR

T1 - Evaluation of in vitro aldose redutase inhibitory activity of 5-arylidene-2,4-thiazolidinediones

AU - Maccari, Rosanna

AU - Ottanà, Rosaria

AU - Ciurleo, Rosella

AU - Vigorita, Maria Gabriella

AU - Rakowitz, Dietmar

AU - Steindl, Theodora

AU - Langer, Thierry

PY - 2007/7/15

Y1 - 2007/7/15

N2 - A number of 5-arylidene-2,4-thiazolidinediones containing a hydroxy or a carboxymethoxy group in their 5-benzylidene moiety have been synthesised and evaluated as in vitro aldose reductase (ALR2) inhibitors. Most of them exhibited strong inhibitory activity, with IC50 values in the range between 0.20 and 0.70 μM. Molecular docking simulations into the ALR2 active site highlighted that the phenolic or carboxylic substituents of the 5-benzylidene moiety can favourably interact, in alternative poses, either with amino acid residues lining the lipophilic pocket of the enzyme, such as Leu300, or with the positively charged recognition region of the ALR2 active site.

AB - A number of 5-arylidene-2,4-thiazolidinediones containing a hydroxy or a carboxymethoxy group in their 5-benzylidene moiety have been synthesised and evaluated as in vitro aldose reductase (ALR2) inhibitors. Most of them exhibited strong inhibitory activity, with IC50 values in the range between 0.20 and 0.70 μM. Molecular docking simulations into the ALR2 active site highlighted that the phenolic or carboxylic substituents of the 5-benzylidene moiety can favourably interact, in alternative poses, either with amino acid residues lining the lipophilic pocket of the enzyme, such as Leu300, or with the positively charged recognition region of the ALR2 active site.

KW - 2,4-Thiazolidinediones

KW - Aldose reductase

KW - Diabetes mellitus

KW - Molecular docking

UR - http://www.scopus.com/inward/record.url?scp=34250337361&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250337361&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2007.04.109

DO - 10.1016/j.bmcl.2007.04.109

M3 - Article

C2 - 17512196

AN - SCOPUS:34250337361

SN - 0960-894X

VL - 17

SP - 3886

EP - 3893

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 14

ER -

Evaluation of in vitro aldose redutase inhibitory activity of 5-arylidene-2,4-thiazolidinediones

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this