Inhibitory activity of IAA and IBA against lipoxygenase: in silico and in vitro validation

被引：3

作者：

Dileep, K. V. ^{[1
,2
]}

Remya, C. ^{[1
,2
]}

Tintu, I. ^{[1
,2
]}

Haridas, M. ^{[1
,2
]}

Sadasivan, C. ^{[1
,2
]}

机构：

[1] Kannur Univ, Dept Biotechnol & Microbiol, Palayad 670661, India

[2] Kannur Univ, Interuniv Ctr Biosci, Palayad 670661, India

来源：

MOLECULAR SIMULATION | 2014年 / 40卷 / 05期

关键词：

LOX; indoleacetic acid; indolebutyric acid; ITC; inducedfit docking; SECRETORY PHOSPHOLIPASE A(2); ALZHEIMERS-DISEASE; INDOLE INHIBITORS; ESCHERICHIA-COLI; CEREBRAL-ISCHEMIA; 5-LIPOXYGENASE; EXPRESSION; BRAIN; SIGNAL; ACID;

D O I：

10.1080/08927022.2013.817671

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070305 [高分子化学与物理];

摘要：

Inhibition of leukotriene biosynthesis is considered to be one of the potential treatment strategies for controlling inflammation, respiratory diseases and many neurodegenerative disorders. Designing of specific functional inhibitors against Lipoxygenases (LOX) has got considerable attention due to its ability to block leukotriene biosynthesis. Molecular docking analysis of two indole derivatives such as indoleacetic acid (IAA) and indolebutyric acid (IBA) are reported here. Both compounds give glide scores better than that of protocatechuic acid and nitro catechol, the two known LOX inhibitors. From the enzyme kinetic analysis, it was revealed that IAA and IBA inhibit competitively. The IC50 values determined for both IAA and IBA were 42.98M and 17.82M, respectively. The binding free energy of these compounds was determined using isothermal titration calorimetric assay and was found to be -6.12kcal/mol for IAA and -7.84kcal/mol for IBA. From the analysis, it can be concluded that both IAA and IBA might be useful as anti-inflammatory agents.

引用

页码：418 / 422

页数：5

共 34 条

[1]

Paralysis and killing of Caenorhabditis elegans by enteropathogenic Escherichia coli requires the bacterial tryptophanase gene [J].

Anyanful, A ;

Dolan-Livengood, JM ;

Lewis, T ;

Sheth, S ;

DeZalia, MN ;

Sherman, MA ;

Kalman, LV ;

Benian, GM ;

Kalman, D .

MOLECULAR MICROBIOLOGY, 2005, 57 (04) :988-1007

[2]

Lipoxygenase interactions with natural flavonoid, quercetin, reveal a complex with protocatechuic acid in its X-ray structure at 2.1 Å resolution [J].

Borbulevych, OY ;

Jankun, J ;

Selman, SH ;

Skrzypczak-Jankun, E .

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2004, 54 (01) :13-19

[3]

Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs [J].

Charlier, C ;

Michaux, C .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2003, 38 (7-8) :645-659

[4]

CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099

[5]

The 5-lipoxygenase enzymatic pathway in the mouse brain:: Young versus old [J].

Chinnici, Cinzia M. ;

Yao, Yuemang ;

Pratico, Domenico .

NEUROBIOLOGY OF AGING, 2007, 28 (09) :1457-1462

[6]

Indole can act as an extracellular signal to regulate biofilm formation of Escherichia coli and other indole-producing bacteria [J].

Di Martino, P ;

Fursy, R ;

Bret, L ;

Sundararaju, B ;

Phillips, RS .

CANADIAN JOURNAL OF MICROBIOLOGY, 2003, 49 (07) :443-449

[7]

Studies of IAA and IBA as fungal a-amylase inhibitors using enzyme kinetics, molecular modeling and thermodynamics [J].

Dileep, Kalarickal V. ;

Tintu, Ignatius ;

Remya, Chandran ;

Haridas, Madathilkovilakathu ;

Sadasivan, Chittalakkottu .

STARCH-STARKE, 2012, 64 (12) :991-995

[8]

Interactions of selected indole derivatives with phospholipase A2: in silico and in vitro analysis [J].

Dileep, Kalarickal Vijayan ;

Remya, Chandran ;

Tintu, Ignatius ;

Haridas, Madathilkovilakathu ;

Sadasivan, Chittalakkottu .

JOURNAL OF MOLECULAR MODELING, 2013, 19 (04) :1811-1817

[9]

Indole inhibitors of human nonpancreatic secretory phospholipase A(2) .1. Indole-3-acetamides [J].

Dillard, RD ;

Bach, NJ ;

Draheim, SE ;

Berry, DR ;

Carlson, DG ;

Chirgadze, NY ;

Clawson, DK ;

Hartley, LW ;

Johnson, LM ;

Jones, ND ;

McKinney, ER ;

Mihelich, ED ;

Olkowski, JL ;

Schevitz, RW ;

Smith, AC ;

Snyder, DW ;

Sommers, CD ;

Wery, JP .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (26) :5119-5136

[10]

Indole inhibitors of human nonpancreatic secretory phospholipase A(2) .3. Indole-3-glyoxamides [J].