Lead Indole-2-carboxyamide Derivative Compounds for Treatment of TB

Unmet Need
Although effective therapy exists for TB caused by drug-susceptible mycobacterium tuberculosis, this therapy requires daily administration of multiple drugs for a minimum of 6 months. The consequence of noncompliance with the existing TB treatment leads to the development of drug-resistant TB in which case both first-line and second-line drug for treating fail. However, a series of compounds just discovered indicates translational potential of novel chemical entities for treatment of both drug-susceptible and drug resistant TB by showing positive lab results in vitro and in vivo experiments. Key advantages of this class of compounds are:

-       The compounds reported have an excellent activity against M. tuberculosis and no apparent cytotoxicity
-       The activity is comparable to that of the most active compounds used for the treatment of actively replicating M. tuberculosis
-       The compound is active also against resistant strains of M. tuberculosis
-       The cross-resistant does not occurs between new discovered compounds and existing first- and second-line drugs
 
Technical Overivew
Johns Hopkins researchers synthesized a class of compounds by employing an efficient amide-coupling protocol. A series of test were run to prove the safety and efficacy of compounds, including MIC, MBC, kill kinetic, cytotoxicity, monotherapy model on TB-infected mice, and in vivo pharmacokinetic evaluation. Furthermore, indoleamide-resistant mutant was identified to rule out the possibility of cross-resistance between existing drugs and discovered drugs. In addition to that, deep sequencing and target identification illustrate the mechanism of drug action. 
 
Looking for Partners: To develop and commercialize the technology as novel treatment for drug-susceptible and drug-resistant TB.
 
Stage of Development
Initial candidate formulation(s) synthesized
 
Publication
doi:10.1038/ncomms3907
     

Category(s):