title: Biological evaluation and molecular modelling study of thiosemicarbazide derivatives as bacterial type IIA topoisomerases inhibitors.
abstract: In the present article, we describe the inhibitory potency of nine thiosemicarbazide derivatives against bacterial type IIA topoisomerases, their antibacterial profile and molecular modelling evaluation. We found that one of the tested compounds, compound 7, significantly inhibits activity of Staphylococcus aureus DNA gyrase with an IC(50) below 15 μM. Besides, this compound displays antibacterial activity on reference Staphylococuss spp. and Enterococcus faecalis strains as well as clinical S. aureus isolates at non-cytotoxic concentrations in mammalian cells with MIC values ranging from 16 to 32 μg/mL thereby indicating, in some cases, equipotent or even more effective action than standard drugs such as vancomycin, ampicillin and nitrofurantoin. The computational studies showed that both molecular geometry and the electron density distribution have a great impact on antibacterial activity of thiosemicarbazide derivatives.
authors: a Department of Organic Chemistry , Medical University of Lublin , Poland .|e Institute of Applied Radiation Chemistry, Lodz University of Technology , Poland.
authors: Agata
authors: A
authors: Paneth
authors: b Department of Microbial Genetics and.
authors: Paweł
authors: P
authors: Stączek
authors: a Department of Organic Chemistry , Medical University of Lublin , Poland .
authors: Tomasz
authors: T
authors: Plech
authors: b Department of Microbial Genetics and.
authors: Aleksandra
authors: A
authors: Strzelczyk
authors: c Department of Immunoparasitology , University of Łódź , Poland .
authors: Katarzyna
authors: K
authors: Dzitko
authors: a Department of Organic Chemistry , Medical University of Lublin , Poland .
authors: Monika
authors: M
authors: Wujec
authors: a Department of Organic Chemistry , Medical University of Lublin , Poland .
authors: Edyta
authors: E
authors: Kuśmierz
authors: d Department of Pharmaceutical Microbiology , Medical University of Lublin , Poland , and.
authors: Urszula
authors: U
authors: Kosikowska
authors: d Department of Pharmaceutical Microbiology , Medical University of Lublin , Poland , and.
authors: Agnieszka
authors: A
authors: Grzegorczyk
authors: e Institute of Applied Radiation Chemistry, Lodz University of Technology , Poland.
authors: Piotr
authors: P
authors: Paneth
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D027081:DNA Gyrase / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II; D004305:Dose-Response Relationship, Drug; D013293:Enterococcus faecalis / Q000187:drug effects / Q000201:enzymology*; D005347:Fibroblasts / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D012663:Semicarbazides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D012663:Semicarbazides; D059005:Topoisomerase II Inhibitors; C005151:thiosemicarbazide; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II
keywords: Antibacterials; bacterial type IIA topoisomerases; molecular modelling; thiosemicarbazide derivatives; toxicity