Benzaldehyde thiosemicarbazone derivatives against replicating and nonreplicating Mycobacterium tuberculosis

Recently, the article dedicated to the development of antituberculosis agents based on benzaldehyde thiosemicarbazone derivatives has been published.

Abstract:

In this article, we report a series of benzaldehyde thiosemicarbazone derivatives possessing high activity toward actively replicating Mycobacterium tuberculosis strain with minimum inhibitory concentration (MIC) values in the range from 0.14 to 2.2 μM. Among them, two compounds - 2-(4-phetethoxybenzylidene)hydrazine-1-carbothiamide (13) and 2-(3-isopropoxybenzylidene)hydrazine-1-carbothiamide (20) also demonstrate submicromolar antimycobacterial activity against M. tuberculosis under hypoxia with MIC values of 0.68 and 0.74 μM, respectively. The activity of compounds 13 and 20 toward five investigated isoniazid-, rifampicin-, and fluoroquinolone-resistant M. tuberculosis isolates is similar to commercially available antituberculosis drugs. The compounds 13 and 20 possess good ADME properties and have low cytotoxicity toward human liver cells (HepG2). Therefore, 2-(4-phenethoxybenzylidene)hydrazine-1-carbothiamide (13) and 2-(3-isopropoxybenzylidene)hydrazine-1-carbothiamide (20) are valuable candidates for further preclinical studies. 

• Benzaldehyde thiosemicarbazone derivatives against replicating and nonreplicating Mycobacterium tuberculosis. Volynets GP, Tukalo MA, Bdzhola VG, Derkach NM, Gumeniuk MI, Tarnavskiy SS, Starosyla SA, Yarmoluk SM. J Antibiot. 2019, 72: 218-224.