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Docking studies on novel alkaloid tryptanthrin and its analogues against enoyl-acyl carrier protein reductase (InhA) of <i>Mycobacterium tuberculosis</i>

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Title Docking studies on novel alkaloid tryptanthrin and its analogues against enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis
 
Creator Tripathi, Ankit
Wadia, Nupur
Bindal, Deepak
Jana, Tarakanta
 
Subject Mycobacterium tuberculosis
Enoyl acyl carrier protein reductase
Natural alkaloid
Tryptanthrin
Molecular docking
 
Description 435-441
Isoniazid resistance is a serious threat in the battle
against the treatment of multi-drug resistant tuberculosis (MDR-TB) and
extremely drug-resistant tuberculosis (XDR-TB). Isoniazid is an inhibitor of
enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis, which
is an important and functional enzyme of the type II fatty acid synthesis
system and important therapeutic target. Natural alkaloid tryptanthrin and its
analogues have shown anti-tubercular activity against
MDR-TB, but their cellular target is unknown. In this work, in silico
molecular docking was performed using docking server in order to see the
interaction of tryptanthrin and its 15 analogues with InhA of M.
tuberculosis. Results showed that among tryptanthrin and its 15 analogues,
tryptanthrin and its two analogues exhibited good affinity to the binding site
of InhA with free binding energy of -7.94 kcal/mol and inhibition constant (Ki)
of 1.50 µm. Active site residues of InhA
interacting with tryptanthrin were Ser13, Thr39, Phe41, Leu63, Asp64, Val65,
Ile95, Phe97 and Ile122. In binding mode, polar bond were found between O1 (1)
with Asp64 of bond length (3.34 Å) and hydrophobic bonds were found between
Leu63 with C15 and C12, Val65 with C7, Val65 with C12 and C4, Ile95 with C6 and
C7, Ile95 with C10, C12 and C14. Important pi-pi bonds were found between Phe41
with C2, C5, C7, C12, C4, C6, C8, C9, C13 and Phe97 with C9. These interactions indicated stability of tryptanthrin
in active residue and suggested it as a potential drug candidate. Thus,
good affinity of tryptanthrin to binding site of InhA may lead to synthesis of
anti-tubercular drug capable of combating MDR strains of M. tuberculosis.
 
Date 2012-12-13T07:26:42Z
2012-12-13T07:26:42Z
2012-12
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/15243
 
Language en_US
 
Rights CC Attribution-Noncommercial-No Derivative Works 2.5 India
 
Publisher NISCAIR-CSIR, India
 
Source IJBB Vol.49(6) [December 2012]