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Selective Mycobacterium tuberculosis Shikimate Kinase Inhibitors as Potential Antibacterials.

Gordon S, Simithy J, Goodwin DC, Calderón AI - Perspect Medicin Chem (2015)

Bottom Line: Many studies have used in silico technology to identify compounds that are anticipated to interact with and inhibit SK.To a much more limited extent, SK inhibition has been evaluated by in vitro methods with purified enzyme.In this review, we present a summary of the progress of SK inhibitor discovery and evaluation with particular attention toward development of new antitubercular agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.

ABSTRACT
Owing to the persistence of tuberculosis (TB) as well as the emergence of multidrug-resistant and extensively drug-resistant (XDR) forms of the disease, the development of new antitubercular drugs is crucial. Developing inhibitors of shikimate kinase (SK) in the shikimate pathway will provide a selective target for antitubercular agents. Many studies have used in silico technology to identify compounds that are anticipated to interact with and inhibit SK. To a much more limited extent, SK inhibition has been evaluated by in vitro methods with purified enzyme. Currently, there are no data on in vivo activity of Mycobacterium tuberculosis shikimate kinase (MtSK) inhibitors available in the literature. In this review, we present a summary of the progress of SK inhibitor discovery and evaluation with particular attention toward development of new antitubercular agents.

No MeSH data available.


Related in: MedlinePlus

Chemical structure of five compounds from ZINC database, which display inhibitory effects for MtSK.
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Related In: Results  -  Collection


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f3-pmc-7-2015-009: Chemical structure of five compounds from ZINC database, which display inhibitory effects for MtSK.

Mentions: In the crystallographic structure 1WE2 of MtSK, the hydrogen bond acceptor is the main chain carbonyl group of Arg 153 with compound ZINC02160785. Analogs of this compound can be synthesized by adding a group to participate in an intermolecular contact with Arg 154 to improve ligand–binding affinity (Fig. 3).


Selective Mycobacterium tuberculosis Shikimate Kinase Inhibitors as Potential Antibacterials.

Gordon S, Simithy J, Goodwin DC, Calderón AI - Perspect Medicin Chem (2015)

Chemical structure of five compounds from ZINC database, which display inhibitory effects for MtSK.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4362912&req=5

f3-pmc-7-2015-009: Chemical structure of five compounds from ZINC database, which display inhibitory effects for MtSK.
Mentions: In the crystallographic structure 1WE2 of MtSK, the hydrogen bond acceptor is the main chain carbonyl group of Arg 153 with compound ZINC02160785. Analogs of this compound can be synthesized by adding a group to participate in an intermolecular contact with Arg 154 to improve ligand–binding affinity (Fig. 3).

Bottom Line: Many studies have used in silico technology to identify compounds that are anticipated to interact with and inhibit SK.To a much more limited extent, SK inhibition has been evaluated by in vitro methods with purified enzyme.In this review, we present a summary of the progress of SK inhibitor discovery and evaluation with particular attention toward development of new antitubercular agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.

ABSTRACT
Owing to the persistence of tuberculosis (TB) as well as the emergence of multidrug-resistant and extensively drug-resistant (XDR) forms of the disease, the development of new antitubercular drugs is crucial. Developing inhibitors of shikimate kinase (SK) in the shikimate pathway will provide a selective target for antitubercular agents. Many studies have used in silico technology to identify compounds that are anticipated to interact with and inhibit SK. To a much more limited extent, SK inhibition has been evaluated by in vitro methods with purified enzyme. Currently, there are no data on in vivo activity of Mycobacterium tuberculosis shikimate kinase (MtSK) inhibitors available in the literature. In this review, we present a summary of the progress of SK inhibitor discovery and evaluation with particular attention toward development of new antitubercular agents.

No MeSH data available.


Related in: MedlinePlus