title: 1,4-Disubstituted thiosemicarbazide derivatives are potent inhibitors of Toxoplasma gondii proliferation.
abstract: A series of 4-arylthiosemicarbazides substituted at the N1 position with a 5-membered heteroaryl ring was synthesized and evaluated in vitro for T. gondii inhibition proliferation and host cell cytotoxicity. At non-toxic concentrations for the host cells all studied compounds displayed excellent anti-parasitic effects when compared to sulfadiazine, indicating a high selectivity of their anti-T. gondii activity. The differences in bioactivity investigated by DFT calculations suggest that the inhibitory activity of 4-aryl-thiosemicarbazides towards T. gondii proliferation is connected with the electronic structure of the molecule. Further, these compounds were tested as potential antibacterial agents. No growth-inhibiting effect on any of the test microorganisms was observed for all the compounds, even at high concentrations.
authors.affiliation: Department of Immunoparasitology, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland. dzika@biol.uni.lodz.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Dzitko
authors.affiliation: Department of Organic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland. piotr.paneth@p.lodz.pl.
authors.forename: Agata
authors.initials: A
authors.lastname: Paneth
authors.affiliation: Department of Organic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland. tomasz.plech@umlub.pl.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Plech
authors.affiliation: Institute for Medical Biology of the Polish Academy of Sciences, Lodowa 106, 93-232 Łódź, Poland. jpawelczyk@cbm.pan.pl.
authors.forename: Jakub
authors.initials: J
authors.lastname: Pawełczyk
authors.affiliation: Department of Genetics of Microorganisms, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland. pstaczek@biol.uni.lodz.pl.
authors.forename: Paweł
authors.initials: P
authors.lastname: Stączek
authors.affiliation: Department of Pharmaceutical Microbiology, Medical University of Warsaw, Oczki 3, 02-007 Warszawa, Poland. jstefanska@wum.edu.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Stefańska
authors.affiliation: Institute of Applied Radiation Chemistry, Technical University of Lodz, Zeromskiego 116, 90-924 Lodz, Poland. piotr.paneth@p.lodz.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Paneth
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D005260:Female; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D012663:Semicarbazides / Q000737:chemistry* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D059005:Topoisomerase II Inhibitors / Q000737:chemistry / Q000494:pharmacology; D014122:Toxoplasma / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D012663:Semicarbazides; D059005:Topoisomerase II Inhibitors; C005151:thiosemicarbazide