title: Search for human DNA topoisomerase II poisons in the group of 2,5-disubstituted-1,3,4-thiadiazoles.
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 compound 2 is a human topoisomerase II (topoII) catalytic inhibitor whereas the two other compounds (i.e. 3 and 4) are capable of stabilizing DNA-topoII cleavage complex and thus are topoII poisons.
authors: a Department of Organic Chemistry , Medical University of Lublin , Chodzki , Lublin , Poland .
authors: Tomasz
authors: T
authors: Plech
authors: a Department of Organic Chemistry , Medical University of Lublin , Chodzki , Lublin , Poland .
authors: Barbara
authors: B
authors: Kaproń
authors: a Department of Organic Chemistry , Medical University of Lublin , Chodzki , Lublin , Poland .
authors: Agata
authors: A
authors: Paneth
authors: a Department of Organic Chemistry , Medical University of Lublin , Chodzki , Lublin , Poland .
authors: Monika
authors: M
authors: Wujec
authors: b Department of Synthesis and Technology of Drugs , Medical University of Białystok , Kilińskiego , Białystok , Poland .
authors: Robert
authors: R
authors: Czarnomysy
authors: c Department of Biotechnology , Medical University of Białystok , Kilińskiego , Białystok , Poland , and.
authors: Anna
authors: A
authors: Bielawska
authors: b Department of Synthesis and Technology of Drugs , Medical University of Białystok , Kilińskiego , Białystok , Poland .
authors: Krzysztof
authors: K
authors: Bielawski
authors: a Department of Organic Chemistry , Medical University of Lublin , Chodzki , Lublin , Poland .
authors: Nazar
authors: N
authors: Trotsko
authors: a Department of Organic Chemistry , Medical University of Lublin , Chodzki , Lublin , Poland .
authors: Edyta
authors: E
authors: Kuśmierz
authors: d Institute of Applied Radiation Chemistry, Lodz University of Technology , Żeromskiego , Lodz , Poland.
authors: Piotr
authors: P
authors: Paneth
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D013830:Thiadiazoles; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II
keywords: 1,3,4-Thiadiazoles; MTT assay; breast cancer; cytotoxicity; topoisomerase inhibitors