4-Substituted picolinohydrazonamides as a new class of potential antitubercular agents

The series of new 4-substituted picolinohydrazonamides were synthesized (6-25) and evaluated for tuberculostatic activity. Compounds having a hydrophilic cyclic amine such as morpholine and pyrrolidine at the end of the thiosemicarbazide chain, exhibited the highest antimycobacterial activity. The a...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2020-03, Vol.190, p.112106, Article 112106
Main Authors: Krause, Malwina, Foks, Henryk, Ziembicka, Dagmara, Augustynowicz-Kopeć, Ewa, Głogowska, Agnieszka, Korona-Głowniak, Izabela, Bojanowski, Krzysztof, Siluk, Danuta, Gobis, Katarzyna
Format: Article
Language:English
Subjects:
Animals
Antitubercular Agents - chemical synthesis
Antitubercular Agents - pharmacology
Antitubercular Agents - toxicity
Bacteria - drug effects
Cytotoxic activity
Humans
Mice
Microbial Sensitivity Tests
Microscopic observation
Molecular Structure
Pyridines - chemical synthesis
Pyridines - pharmacology
Pyridines - toxicity
Synthesis
Thiosemicarbazide
Thiosemicarbazones - chemical synthesis
Thiosemicarbazones - pharmacology
Thiosemicarbazones - toxicity
Tuberculosis
Yeasts - drug effects
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Summary:The series of new 4-substituted picolinohydrazonamides were synthesized (6-25) and evaluated for tuberculostatic activity. Compounds having a hydrophilic cyclic amine such as morpholine and pyrrolidine at the end of the thiosemicarbazide chain, exhibited the highest antimycobacterial activity. The antimycobacterial activity of compounds 6, 11, and 15 (MIC 0.4–0.8 μg/mL) was higher than that of reference drugs. Moreover, derivative 15 exhibited lower activity against other tested microorganism such as bacteria gram-positive, gram-negative or fungi. Thus, this compound is characterized by the selectivity of antimicrobial activity. Antiproliferative study conducted against human dermal fibroblasts (HDF) and mouse melanoma cell line (B16-F10) revealed low cytotoxicity of compound 15. Conducted research allowed to identify compound 15 as leading for further research. [Display omitted] •A series of 4-substituted picolinohydrazonamide derivatives were synthesized.•Compounds were tested for their tuberculostatic and antimicrobial activity.•Cytotoxic activity against human dermal fibroblasts and mouse melanoma cells was determined.•Compound 15 is selected as good leading structure for further studies.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2020.112106