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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

Molecular structures of shikimic acid analogues.
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Related In: Results  -  Collection


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f4-pmc-7-2015-009: Molecular structures of shikimic acid analogues.

Mentions: Using structural and molecular dynamics simulation studies, Blanco et al.29 designed shikimic acid analogs that would bind to the shikimate binding site and determined experimental measurements of inhibition constants. Seven shikimic acid analogs (Fig. 4) were assayed and shown to be reversible competitive inhibitors and bind to the same binding site as shikimic acid. The KI values (Table 5), obtained by Dixon plots (1/v vs [I]), ranged from 46 μM to >4000 μM with compound 660 being the most potent inhibitor.


Selective Mycobacterium tuberculosis Shikimate Kinase Inhibitors as Potential Antibacterials.

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

Molecular structures of shikimic acid analogues.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-pmc-7-2015-009: Molecular structures of shikimic acid analogues.
Mentions: Using structural and molecular dynamics simulation studies, Blanco et al.29 designed shikimic acid analogs that would bind to the shikimate binding site and determined experimental measurements of inhibition constants. Seven shikimic acid analogs (Fig. 4) were assayed and shown to be reversible competitive inhibitors and bind to the same binding site as shikimic acid. The KI values (Table 5), obtained by Dixon plots (1/v vs [I]), ranged from 46 μM to >4000 μM with compound 660 being the most potent inhibitor.

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