Perchlozone®, a new thiosemicarbazone class drug, was approved for treatment of multidrug-resistant tuberculosis (MDR-TB) in Russia in 2012. The mechanism of action of the drug was at the time unknown.
Another thiosemicarbazone is a well-studied old TB drug thiacetazone. It is known to inhibit the FASII dehydratase complex HadABC, which is involved in cell wall biosynthesis in Mycobacterium tuberculosis. Thiosemicarbazone is a prodrug requiring activation by the monooxygenase EthA.
SPRINT-TB Theme 1 performed a comparative in vitro analysis of both drugs. The two compounds were found to have an identical spectrum of activity. Spontaneous drug-resistant mutants exibited cross-resistance, which was mapped to HadABC and EthA, thereby suggesting that perchlozone, like thiacetazone, is activated by EthA with its principal target being HadABC.
The study was published in the International Journal of Antimicrobial Agents in April 2015 (Gopal P, Dick T. The new tuberculosis drug Perchlozone shows cross-resistance with Thiacetazone. Int J Antimicrob Agents. 2015 Apr;45(4):430-3.)
Another thiosemicarbazone is a well-studied old TB drug thiacetazone. It is known to inhibit the FASII dehydratase complex HadABC, which is involved in cell wall biosynthesis in Mycobacterium tuberculosis. Thiosemicarbazone is a prodrug requiring activation by the monooxygenase EthA.
SPRINT-TB Theme 1 performed a comparative in vitro analysis of both drugs. The two compounds were found to have an identical spectrum of activity. Spontaneous drug-resistant mutants exibited cross-resistance, which was mapped to HadABC and EthA, thereby suggesting that perchlozone, like thiacetazone, is activated by EthA with its principal target being HadABC.
The study was published in the International Journal of Antimicrobial Agents in April 2015 (Gopal P, Dick T. The new tuberculosis drug Perchlozone shows cross-resistance with Thiacetazone. Int J Antimicrob Agents. 2015 Apr;45(4):430-3.)
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