Title:Dual Antibacterial and Anticancer Activity of 4-Benzoyl-1-dichlorobenzoylthiosemicarbazide Derivatives
VOLUME: 18 ISSUE: 4
Author(s):Barbara Kapron, Robert Czarnomysy, Agata Paneth, Monika Wujec, Krzysztof Bielawski, Anna Bielawska, Lukasz Swiatek, Barbara Rajtar, Malgorzata Polz-Dacewicz and Tomasz Plech*
Affiliation:Department of Organic Chemistry, Medical University of Lublin, Chodzki 4A, 20-093 Lublin, Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Department of Organic Chemistry, Medical University of Lublin, Chodzki 4A, 20-093 Lublin, Department of Organic Chemistry, Medical University of Lublin, Chodzki 4A, 20-093 Lublin, Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Department of Biotechnology, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Department of Virology, Faculty of Medicine, Medical University, Chodzki 1, 20-093 Lublin, Department of Virology, Faculty of Medicine, Medical University, Chodzki 1, 20-093 Lublin, Department of Virology, Faculty of Medicine, Medical University, Chodzki 1, 20-093 Lublin, Department of Pharmacology, Medical University of Lublin, Chodzki 4a, 20-093 Lublin
Keywords:Human DNA topoisomerase, MTT assay, [3H]-thymidine incorporation assay, breast cancer cells head and neck
squamous cell carcinomas (HNSCC).
Abstract:Objective/Method: A group of 4-benzoyl-1-dichlorobenzoylthiosemicarbazides endowed
with antibacterial activity was evaluated for its cytotoxic properties against breast cancer cells (MCF-7,
MDA-MB-231) and head and neck squamous cell carcinomas (FaDu, SCC-25). Cytotoxicity of the investigated
compounds was measured using MTT and [3H]-thymidine incorporation bioassays.
Result: 1-(2,3-Dichlorobenzoyl)-4-(2-methylbenzoyl)thiosemicarbazide (TA-4), 1-(2,4-dichlorobenzoyl)-
4-(2-methylbenzoyl)thiosemicarbazide (TA-18), and 1-(2,4-dichlorobenzoyl)-4-(4-nitrolbenzoyl)-
thiosemicarbazide (TA-20) were found to possess anticancer activity equipotent or even stronger than
that of reference drug – etoposide. In order to clarify the molecular mode of action of the mentioned
compounds, the relaxation assay kit for human DNA topoisomerase II was used. It turned out that reduction
of viability of cancer cells was a result of inhibition of human DNA topoII. Molecular docking
studies proved that 4-benzoyl-1-dichlorobenzoylthiosemicarbazides strongly interact with DNAdependent
subunit of that enzyme.
