Benzaldehyde thiosemicarbazone derivatives against replicating and nonreplicating Mycobacterium tuberculosis

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-phenethoxybenzy...

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Bibliographic Details
Published in:Journal of antibiotics 2019-04, Vol.72 (4), p.218-224
Main Authors: Volynets, Galyna P., Tukalo, Michail A., Bdzhola, Volodymyr G., Derkach, Nataliia M., Gumeniuk, Mykola I., Tarnavskiy, Sergiy S., Starosyla, Sergiy A., Yarmoluk, Sergiy M.
Format: Article
Language:English
Subjects:
631/326/22/1290
692/699/255/1856
Antitubercular Agents - chemical synthesis
Antitubercular Agents - pharmacology
Antitubercular Agents - toxicity
Bacteriology
Benzaldehydes - chemical synthesis
Benzaldehydes - pharmacology
Benzaldehydes - toxicity
Biomedical and Life Sciences
Bioorganic Chemistry
Cell Survival - drug effects
Cytotoxicity
Hep G2 Cells
Hepatocytes - drug effects
Hepatocytes - physiology
Humans
Hypoxia
Life Sciences
Medicinal Chemistry
Microbial Sensitivity Tests
Microbiology
Molecular Structure
Mycobacterium tuberculosis - drug effects
Organic Chemistry
Thiosemicarbazones - chemical synthesis
Thiosemicarbazones - pharmacology
Thiosemicarbazones - toxicity
Tuberculosis
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Summary: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-phenethoxybenzylidene)hydrazine-1-carbothioamide ( 13 ) and 2-(3-isopropoxybenzylidene)hydrazine-1-carbothioamide ( 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-carbothioamide ( 13 ) and 2-(3-isopropoxybenzylidene)hydrazine-1-carbothioamide ( 20 ) are valuable candidates for further preclinical studies.
ISSN:0021-8820
1881-1469
DOI:10.1038/s41429-019-0140-9