2. Academic Validation
  3. 4-Substituted picolinohydrazonamides as a new class of potential antitubercular agents

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

  • Eur J Med Chem. 2020 Mar 15;190:112106. doi: 10.1016/j.ejmech.2020.112106.
Malwina Krause 1,  Henryk Foks 1,  Dagmara Ziembicka 1,  Ewa Augustynowicz-Kopeć 2,  Agnieszka Głogowska 2,  Izabela Korona-Głowniak 3,  Krzysztof Bojanowski 4,  Danuta Siluk 5,  Katarzyna Gobis 6
Affiliations

Affiliations

  • 1 Department of Organic Chemistry, Medical University of Gdańsk, Gdańsk, Poland.
  • 2 Department of Microbiology, Institute of Tuberculosis and Pulmonary Diseases, Warsaw, Poland.
  • 3 Department of Pharmaceutical Microbiology, Medical University of Lublin, Lublin, Poland.
  • 4 Sunny BioDiscovery Inc., Santa Paula, CA, 93060, USA.
  • 5 Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Poland.
  • 6 Department of Organic Chemistry, Medical University of Gdańsk, Gdańsk, Poland. Electronic address: [email protected].
PMID: 32061963 DOI: 10.1016/j.ejmech.2020.112106
Abstract

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.

Keywords

Cytotoxic activity; Microscopic observation; Synthesis; Thiosemicarbazide; Tuberculosis.

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