Record Details

Investigating the inhibitory potential of 2-Aminopurine metal complexes against serine/threonine protein kinases from Mycobacterium tuberculosis.

IR@CSIR-CFTRI

View Archive Info
 
 
Field Value
 
Relation http://ir.cftri.com/13407/
https://doi.org/10.1016/j.tube.2017.10.005
 
Title Investigating the inhibitory potential of 2-Aminopurine metal complexes against
serine/threonine protein kinases from Mycobacterium tuberculosis.
 
Creator Vaibhav Singh, Bais
Balaram, Mohapatra
Nadim, Ahamad
Sanjana, Boggaram
Sandeep, Verma
Balaji, Prakash
 
Subject 01 Medical sciences
05 Enzymes
 
Description Tuberculosis – a disease caused by Mycobacterium tuberculosis (Mtb), is one of the most
devastating. The discovery of Ser/Thr protein kinases (STPKs) in Mtb opened a new avenue for
developing anti-tubercular inhibitors. The in-vivo inhibitory effects of many metal ions have
been demonstrated in literature. But, one of the limitations of metal ions as inhibitors is their
inability to traverse the hydrophobic membrane due to polar nature and their propensity for nonspecific
interactions. To overcome this, we attached a metal ion to 2-A9P – an analog derived
from a cell permeable scaffold, 2-Aminopurine (2-AP) which is a known kinase inhibitor. We
investigated the inhibitory potential of 2-AP and its analog 2-A9P against protein kinase B
(PknB) and showed that both of these can inhibit Mtb STPKs. Next, we evaluated the latent
inhibitory activity of metal ions and for the first time showed that they can inhibit the
phosphotransfer reaction in PknB, PknG and PknL. Subsequently, 6 different metal complexes
(MC) of 2-A9P were used for inhibitory studies and their estimated IC50 values show that most
MCs inhibited PknB with low micromolar potency. Further, MIC values determined for the six
MCs against Mtb showed that MC-4 and MC-6 exhibit whole cell inhibitory activity.
Cytotoxicity studies show that MC-4 and MC-6 do not affect cell viability of A549 cell lines,
suggesting that these inhibitors can be further developed as anti-tubercular agents.
 
Date 2018
 
Type Article
PeerReviewed
 
Format pdf
 
Language en
 
Identifier http://ir.cftri.com/13407/1/Tuberculosis%202017.pdf
Vaibhav Singh, Bais and Balaram, Mohapatra and Nadim, Ahamad and Sanjana, Boggaram and Sandeep, Verma and Balaji, Prakash (2018) Investigating the inhibitory potential of 2-Aminopurine metal complexes against serine/threonine protein kinases from Mycobacterium tuberculosis. Tuberculosis, 108. pp. 47-55.