Čes. slov. farm. 2020, 69(5):203-210 | DOI: 10.36290/csf.2020.028

Focus on perchlozone, an anti-tuberculosis drug from the Russian Federation

Ivan Malík^1,2,*, Jozef Čižmárik¹, Mária Pecháčová¹

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Slovak Republic

² Institute of Chemistry, Clinical Biochemistry and Laboratory, Medicine, Faculty of Medicine, Slovak Medical University in Bratislava, Slovak Republic

The prevalence of multidrug-resistant tuberculosis (MDR--TB) and extensively drug-resistant tuberculosis (XDR--TB) has been increasing at an alarming rate worldwide. Today's "Fight against Tuberculosis" programmes in the Russian Federation are subsidized by state and regional governments as well as health authorities. Each region has its own specific characteristics and needs specific interventions. Although some novel anti-tuberculosis (anti-TB) drugs (

bedaquiline,

delamanid) were approved by relevant authorities, and some promising compounds, especially those of oxazolidinones, are in various phases of clinical trials worldwide, the finding of effective, safe, pharmacokinetically favo-rable, economically and logistically accessible anti-TB agents still remains a serious challenge for medical and pharmaceutical sciences.

Perchlozone, a compound containing a thiosemicarbazone scaffold, was approved in the Russian Federation in 2012 for the treatment (alone or as the active component of complex treatment regimens) of HIV-1 negative as well as HIV-1 positive patients suffering from MDR-TB or XDR-TB. Mechanism of anti-TB action of

perchlozone might be similar to that of

thiacetazone, which belongs into the same chemical class.

Perchlozone has to be probably activated into reactive species by a mycobacterially encoded monoxygenase (EthA). The activated forms might act in multiple ways, including inhibition of mycobacterial cell wall synthesis due to interfence with a dehydration step of the type II fatty acid synthase pathway or sensitization of the Mycobacterium tuberculosis cell to oxidative stress. Favorable toxicological properties of

perchlozone and its tolerability by the human organism were confirmed within revevant preclinical and clinical studies. However, recent preliminary investigations in vivo (animal models) could indicate genotoxicity after subacute inhalation of the drug. Regarding this issue, further development of more convenient nano- or microparticle-based formulations of

perchlozone potentially improving targeted delivering and efficiency as well as decreasing (eliminating) its eventual toxicity might be taken into strong consideration.

Keywords: perchlozone; Mycobacterium tuberculosis; resistance; MDR-TB; XDR-TB; HIV-1 co-infection

Received: September 23, 2020; Accepted: October 7, 2020; Published: May 1, 2020  Show citation