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

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

Volume: 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

Affiliation:

• Department of Biochemistry, Medical University of Warszawa, Banacha 1 Street, 02-097 Warszawa,Poland

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

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.

Cite this article as:

Bielenica Anna*, Stepien Karolina, Sawczenko Aleksandra, Lis Tadeusz, Koziol E. Anna, Madeddu Silvia, Collu David, Iuliano Filippo, Kosmider Anita and Struga Marta, Synthesis, Structural Studies and Biological Evaluation of Halogen Derivatives of 1,3-Disubstituted Thiourea, Letters in Drug Design & Discovery 2017; 14 (6) . https://dx.doi.org/10.2174/1570180814666170106121025

DOI https://dx.doi.org/10.2174/1570180814666170106121025	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X