SEARCH FOR NEW ANTITUBERCULAR DRUGS AMONG THE SALTS AND BASES OF O-AROYLATION PRODUCTS OF β-(THIOMORFOLIN-1-YL)- AND β-(4-METHYLPIPERAZIN-1-YL) PROPIOAMIDOXIMES

Abstract

Tuberculosis (TB) is the leading cause of death and morbidity in more than one third of the world's population. The incidence of tuberculosis in Kazakhstan over the past 10 years has decreased to 52,2 per 100 thousand population (2017) against 126,4 per 100 thousand population in 2007; mortality rate – in 6 times, reaching 3,0 per 100 thousand of population (2017). In order to reduce the duration of treatment, exclude the rapid development of drug resistance, toxic and side effects of existing anti-TB drugs and to reduce the cost of extremely expensive treatment of TB (DS, MDR, XDR), the world is searching for new TB drugs. We have synthesized the salts and bases of the O-aroylation products of β-(thiomorpholin-1-yl) and β-(4-methylpiperazin-1-yl) propioamidoximes, containing in the β-position pharmacophore fragments of 1-methylpiperazine and thiomorpholine. In vitro anti-tuberculosis screening of β-aminopropioamidoxime derivatives in the DS, DR and MDR strains of M. tuberculosis revealed highly active competitive compounds which are less toxic than rifampicin and isoniazid with activity significantly exceeding the activity of the reference preparations. It is assumed that these compounds may be the subject of subsequent trials in the development of doses and new treatment regimens for TB.

References

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