Selective Mycobacterium tuberculosis Shikimate Kinase Inhibitors as Potential Antibacterials.

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Microbiology

Background:

• Tuberculosis (TB) remains a global health challenge, exacerbated by multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains.
• The development of novel antitubercular agents is critical to combat persistent and resistant forms of TB.
• The shikimate pathway, essential for Mycobacterium tuberculosis survival, presents a promising target for drug development.

Purpose of the Study:

• To review the progress in discovering and evaluating shikimate kinase (SK) inhibitors as potential antitubercular agents.
• To highlight the importance of targeting Mycobacterium tuberculosis shikimate kinase (MtSK) for novel drug development.
• To summarize current in silico and in vitro approaches and identify gaps in in vivo evaluation.

Main Methods:

• In silico screening and computational modeling to identify potential SK inhibitors.
• In vitro enzyme inhibition assays using purified Mycobacterium tuberculosis shikimate kinase (MtSK).
• Literature review of existing studies on SK inhibitor discovery and evaluation.

Main Results:

• Numerous compounds have been identified computationally for their potential to inhibit SK.
• In vitro studies have demonstrated the feasibility of inhibiting purified MtSK.
• A significant gap exists in the literature regarding the in vivo efficacy of MtSK inhibitors.

Conclusions:

• Shikimate kinase (SK) is a validated and selective target for developing new antitubercular drugs.
• While in silico and in vitro methods have advanced inhibitor discovery, in vivo validation is crucial.
• Further research into the in vivo activity of MtSK inhibitors is necessary for clinical translation.