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Molecules. 2019 Jan 11;24(2). pii: E251. doi: 10.3390/molecules24020251.

Synthesis, In Vitro Screening and Docking Studies of New Thiosemicarbazide Derivatives as Antitubercular Agents.

Author information

1
Independent Radiopharmacy Unit, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 20-093 Lublin, Poland. monika.pitucha@umlub.pl.
2
Faculty of Science, Siedlce University of Natural Sciences and Humanities, 08-110 Siedlce, Poland. kar@uph.edu.pl.
3
Department of Biochemistry and Biotechnology, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 20-093 Lublin, Poland. martaswatkoossor@umlub.pl.
4
Faculty of Science, Siedlce University of Natural Sciences and Humanities, 08-110 Siedlce, Poland. wwysocki@uph.edu.pl.
5
Independent Radiopharmacy Unit, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 20-093 Lublin, Poland. wos.maciej@gmail.com.
6
Independent Radiopharmacy Unit, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 20-093 Lublin, Poland. kamilchudzik@umlub.pl.
7
Department of Biochemistry and Biotechnology, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 20-093 Lublin, Poland. grazyna.ginalska@umlub.pl.
8
Institute of General and Ecological Chemistry, Technical University, 90-924 Łódź, Poland. andrzej.fruzinski@p.lodz.pl.

Abstract

A series of thiosemicarbazide derivatives was designed and synthesized by reaction of carboxylic acid hydrazide with isothiocyanates. The molecular structures of the investigated thiosemicarbazides were confirmed and characterized by spectroscopic analysis. The conformational preference of carbonylthiosemicarbazide chain and intra- and intermolecular interactions in the crystalline state were characterized using X-ray analysis. The antituberculosis activity of the target compounds were tested in vitro against four Mycobacterium strains: M. H37Ra, M. phlei, M. smegmatis, M. timereck. The most active compounds were those with 2-pyridine ring. They exhibited lower minimal inhibitory concentration (MIC) values in the range 7.81⁻31.25 μg/mL in comparison to the other isomers. Compound 5 had activity against M. smegmatis at a concentration of 7.81 μg/mL whereas compound 2 had activity against all tested strains at a concentration of 15.625 μg/mL. The molecular docking studies were performed for investigated compounds using the Mycobacterium tuberculosis glutamine synthetase MtGS as their molecular target.

KEYWORDS:

X-ray analysis; molecular docking; synthesis; thiosemicarbazide; tuberculosis

PMID:
30641902
PMCID:
PMC6359303
DOI:
10.3390/molecules24020251
[Indexed for MEDLINE]
Free PMC Article

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