title: Design, synthesis and biological evaluation of 4-benzoyl-1-dichlorobenzoylthiosemicarbazides as potent Gram-positive antibacterial agents.
abstract: Twelve 4-benzoyl-1-dichlorobenzoylthiosemicarbazides have been tested as potential antibacterials. All the compounds had MICs between 0.49 and 15.63 µg/ml toward Micrococcus luteus, Bacillus cereus, Bacillus subtilis and Staphylococcus epidermidis indicating, in most cases, equipotent or even more effective action than cefuroxime. In order to clarify if the observed antibacterial effects are universal, further research were undertaken to test inhibitory potency of two most potent compounds 3 and 11 on clinical isolates of Staphylococcus aureus. Compound 11 inhibited the growth of methicillin-sensitive S. aureus (MSSA) at MICs of 1.95-7.81 µg/ml, methicillin-resistant S. aureus (MRSA) at MICs of 0.49-1.95 µg/ml and MDR-MRSA at MIC of 0.98 and 3.90 µg/ml, respectively. Finally, inhibitory efficacy of 3 and 11 on planktonic cells and biofilms formation in clinical isolates of S. aureus and Haemophilus parainfluenzae was tested. The majority of cells in biofilm populations of MSSA and MRSA were eradicated at low level of 3, with MBICs in the range of 7.82-15.63 µg/ml.
authors.affiliation: a Department of Organic Chemistry and.
authors.forename: Agata
authors.initials: A
authors.lastname: Paneth
authors.affiliation: a Department of Organic Chemistry and.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Plech
authors.affiliation: a Department of Organic Chemistry and.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kaproń
authors.affiliation: a Department of Organic Chemistry and.
authors.forename: Dominika
authors.initials: D
authors.lastname: Hagel
authors.affiliation: b Department of Pharmaceutical Microbiology , Medical University of Lublin , Lublin , Poland .
authors.forename: Urszula
authors.initials: U
authors.lastname: Kosikowska
authors.affiliation: a Department of Organic Chemistry and.
authors.forename: Edyta
authors.initials: E
authors.lastname: Kuśmierz
authors.affiliation: c Department of Immunoparasitology , University of Łódź , Łódź , Poland , and.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Dzitko
authors.affiliation: d Institute of Applied Radiation Chemistry , Lodz University of Technology , Lodz , Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Paneth
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D012663:Semicarbazides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D012663:Semicarbazides; C005151:thiosemicarbazide
keywords: Antibacterial activity; MDR–MRSA; MRSA; MSSA; anti-biofilm activity; thiosemicarbazide derivatives; toxicity