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Synthesis, Structural Studies and Biological Evaluation of Halogen Derivatives of 1,3-Disubstituted Thiourea

[ Vol. 14 , Issue. 6 ]

Author(s):

Anna Bielenica, Karolina Stepien, Aleksandra Sawczenko, Tadeusz Lis, Anna E. Koziol, Silvia Madeddu, David Collu, Filippo Iuliano, Anita Kosmider and Marta Struga   Pages 636 - 646 ( 11 )

Abstract:


Background: Halogen-substituted thiourea derivatives exert well-documented antimicrobial, antiviral and anticancer properties.

Objective: This work evaluates antimicrobial and cytotoxic activities of newly synthesized fluorinated thiourea compounds.

Method: Two series of thioureas were obtained by the condensation reaction of 4-amino-1- benzylpiperidine (1a-14a) or furfurylamine (1b-14b) and fluorinated isothiocyanates. The anti HIV- 1 activity evaluation was based on inhibition of virus-induced cytopathogenicity in exponentially growing MT-4 cell, determined by the MTT method. Antibacterial potency was examined by the disc-diffusion method under standard conditions using Mueller-Hinton II agar medium according to CLSI guidelines. Antifungal effects were assessed using Mueller-Hinton agar and 2% glucose and 0.5μg/mL Methylene Blue Dye Medium. The viability of HaCaT and A549 cells was assessed by determination of MTT salt conversion by mitochondrial dehydrogenase, whereas release of lactate dehydrogenase from the cytosol to culture medium was a marker of the cell death.

Results: The X-ray crystallography studies showed the conformations adopted by the molecules 2a, 7a, 2b and 7b. Compounds 1a and 14a proved cytotoxic against MT-4 cells and different other cell lines derived from human haematological tumors (CC50 < 10 μM). They influenced on viability, mortality and the growth rate of healthy HaCaT cells. Derivatives 1a, 6a and 2b exhibited moderate activity against Gram-positive bacteria (MIC values 8-128 μg/ml).

Conclusion: The results indicate that new 1,3-disubstituted thioureas exert moderate in vitro antimicrobial and cytotoxic effects.

Keywords:

Thiourea derivatives, cytotoxicity, antitumor activity, X-ray crystallography, HaCaT cells, A549 cells.

Affiliation:

Department of Biochemistry, Medical University of Warszawa, Banacha 1 Street, 02-097 Warszawa, Department of Pharmaceutical Microbiology, Medical University of Warsaw, 02-007 Warszawa, Faculty of Chemistry, Maria Curie-Sklodowska University, 20-031 Lublin, Faculty of Chemistry, University of Wroclaw, 50-353 Wroclaw, Faculty of Chemistry, Maria Curie-Sklodowska University, 20-031 Lublin, Department of Biomedical Sciences, Section of Microbiology and Virology, University of Cagliari, 09042 Cittadella Universitaria Monserrato, Cagliari, Department of Life and Environmental Sciences, Section of Microbiology and Virology, University of Cagliari, 09042 Cittadella Universitaria Monserrato, Cagliari, Department of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Bratislava, Department of Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warszawa, Department of Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warszawa

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