Search for human DNA topoisomerase II poisons in the group of 2, 5-disubstituted-1, 3, 4-thiadiazoles. (2nd November 2015)

• Record Type: Journal Article
• Authors: Plech, Tomasz; Kaproń, Barbara; Paneth, Agata; Wujec, Monika; Czarnomysy, Robert; Bielawska, Anna; Bielawski, Krzysztof; Trotsko, Nazar; Kuśmierz, Edyta; Paneth, Piotr
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 30:Number 6(2015:Dec.)
• Page Start: 1021
• Page End: 1026
• Publication Date: 2015-11-02
• Subjects: 1, 3, 4-Thiadiazoles -- breast cancer -- cytotoxicity -- MTT assay -- topoisomerase inhibitors; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2014.995179
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: A series of six 2, 5-disubstituted 1, 3, 4-thiadiazole derivatives was synthesized and examined for cytotoxic activity in MCF-7 and MDA-MB-231 breast cancer cells. MTT assay confirmed that 2-(3-fluorophenylamino)-5-(3-hydroxyphenyl)-1, 3, 4-thiadiazole (2 ), 2-(4-bromophenylamino)-5-(2, 4-dichlorophenyl)-1, 3, 4-thiadiazole (3 ), 2-(4-fluorophenylamino)-5-(2, 4-dichlorophenyl)-1, 3, 4-thiadiazole (4 ), had ability to inhibit MCF-7 and MDA-MB-231 cells proliferation. The IC50 values for the mentioned compounds ranged between 120 and 160 μM (with respect to MCF-7 cells) and from 70 to 170 μM (with respect to MDA-MB-231 cells). It turned out, moreover, that compound2 is a human topoisomerase II (topoII) catalytic inhibitor whereas the two other compounds (i.e.3 and4 ) are capable of stabilizing DNA-topoII cleavage complex and thus are topoII poisons.