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 | Tomasz Plech, Barbara Kaproń, Agata Paneth, Monika Wujec, Robert Czarnomysy, Anna Bielawska, Krzysztof Bielawski, Nazar Trotsko, Edyta Kuśmierz, Piotr Paneth |
Journal | Journal 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 |
PMID | 25792499
(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
|