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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.
AuthorsTomasz Plech, Barbara Kaproń, Agata Paneth, Monika Wujec, Robert Czarnomysy, Anna Bielawska, Krzysztof Bielawski, Nazar Trotsko, Edyta Kuśmierz, Piotr Paneth
JournalJournal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 30 Issue 6 Pg. 1021-6 (Dec 2015) ISSN: 1475-6374 [Electronic] England
PMID25792499 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents
  • Thiadiazoles
  • Topoisomerase II Inhibitors
  • DNA Topoisomerases, Type II
Topics
  • Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
  • Cell Proliferation (drug effects)
  • DNA Topoisomerases, Type II (metabolism)
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • MCF-7 Cells
  • Molecular Docking Simulation
  • Molecular Structure
  • Structure-Activity Relationship
  • Thiadiazoles (chemical synthesis, chemistry, pharmacology)
  • Topoisomerase II Inhibitors (chemical synthesis, chemistry, pharmacology)
  • Tumor Cells, Cultured

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