The new tuberculosis drug Perchlozone® shows cross-resistance with thiacetazone.

Abstract

Perchlozone(®) (PCZ), a new thiosemicarbazone developed by JSC Pharmasyntez (Moscow, Russia) for the treatment of tuberculosis (TB), was approved for use against multidrug-resistant disease in Russia in 2012. The mechanism of action of the drug is unknown. A well-studied thiosemicarbazone is the old TB drug thiacetazone (TAC). It has a narrow spectrum and inhibits the FASII dehydratase complex HadABC, which is involved in cell wall biosynthesis in Mycobacterium tuberculosis. TAC is a prodrug, requiring activation by the monooxygenase EthA. In this study, a comparative in vitro analysis of both drugs was performed. The two compounds had an identical spectrum of activity, spontaneous resistant mutants showed cross-resistance, and resistance was mapped to HadABC and EthA. These results suggest that PCZ, like TAC, is a prodrug and that both drugs share EthA as an activating enzyme and HadABC as their principal target.

• Authors: Pooja Gopal, Thomas Dick
• Journal: International journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 45 Issue 4 Pg. 430-3 (Apr 2015) ISSN: 1872-7913 [Electronic] Netherlands
• PMID: 25704063 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Chemical References

• Antitubercular Agents
• Thiosemicarbazones
• Oxidoreductases
• ethA protein, Mycobacterium tuberculosis
• Thioacetazone

Topics

• Antitubercular Agents (pharmacology)
• Drug Resistance, Bacterial
• Mutation
• Mycobacterium tuberculosis (drug effects)
• Oxidoreductases (genetics)
• Thioacetazone (pharmacology)
• Thiosemicarbazones (pharmacology)