4-苯甲酰基-1-二氯苯甲酰基硫代氨基脲衍生物的双重抗菌和抗癌活性
Dual Antibacterial and Anticancer Activity of 4-Benzoyl-1-dichlorobenzoylthiosemicarbazide Derivatives.
作者信息
Kapron Barbara, Czarnomysy Robert, Paneth Agata, Wujec Monika, Bielawski Krzysztof, Bielawska Anna, Swiatek Lukasz, Rajtar Barbara, Polz-Dacewicz Malgorzata, Plech Tomasz
机构信息
Department of Organic Chemistry, Medical University of Lublin, Chodzki 4A, 20-093 Lublin, Poland.
Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.
出版信息
Anticancer Agents Med Chem. 2018;18(4):529-540. doi: 10.2174/1871520617666171023142958.
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.
目的/方法：对一组具有抗菌活性的4-苯甲酰基-1-二氯苯甲酰基硫代氨基脲进行评估，检测其对乳腺癌细胞（MCF-7、MDA-MB-231）和头颈部鳞状细胞癌（FaDu、SCC-25）的细胞毒性。使用MTT和[3H]-胸腺嘧啶核苷掺入生物测定法测量所研究化合物的细胞毒性。
结果
发现1-(2,3-二氯苯甲酰基)-4-(2-甲基苯甲酰基)硫代氨基脲（TA-4）、1-(2,4-二氯苯甲酰基)-4-(2-甲基苯甲酰基)硫代氨基脲（TA-18）和1-(2,4-二氯苯甲酰基)-4-(4-硝基苯甲酰基)硫代氨基脲（TA-20）具有与参考药物依托泊苷相当甚至更强的抗癌活性。为了阐明上述化合物的分子作用模式，使用了人DNA拓扑异构酶II松弛测定试剂盒。结果表明，癌细胞活力的降低是抑制人DNA拓扑异构酶II的结果。分子对接研究证明，4-苯甲酰基-1-二氯苯甲酰基硫代氨基脲与该酶的DNA依赖性亚基强烈相互作用。
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