Design and evaluation of biological activities of 1,3‐oxazolidinone derivatives bearing amide, sulfonamide, and thiourea moieties

1,3‐Oxazolidine‐2‐one is an important heterocyclic ring participating in the chemical structure of many drugs. In this research, 22 new amide/sulfonamide/thiourea derivatives (1–22) were obtained by the reaction of (S)‐4‐(4‐aminobenzyl)‐2(1H)‐1,3‐oxazolidinone with 4‐substituted benzoyl chlorides, 4...

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Bibliographic Details
Published in:Archiv der Pharmazie (Weinheim) 2018-09, Vol.351 (9), p.e1800057-n/a
Main Authors: Karaman, Nurcan, Adil Zainel, Rabeah, Kapkaç, Handan A., Karaca Gençer, Hülya, Ilgın, Sinem, Karaduman, A. Burak, Karaküçük‐İyidoğan, Ayşegül, Oruç‐Emre, Emine E., Koçyiğit‐Kaymakçıoğlu, Bedia
Format: Article
Language:English
Subjects:
1,3‐oxazolidine‐2‐one
Amides - chemistry
Amides - pharmacology
Animals
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Antibiotics
antimicrobial activity
Antimicrobial agents
Cell Membrane - drug effects
Cell Survival - drug effects
Dose-Response Relationship, Drug
Drug Design
flow cytometry
Gram-Positive Bacteria - cytology
Gram-Positive Bacteria - drug effects
Male
Mice
Microbial Sensitivity Tests
Microsomes, Liver - drug effects
Microsomes, Liver - metabolism
Microsomes, Liver - microbiology
Molecular Structure
NIH 3T3 Cells
Oxazolidinones - chemical synthesis
Oxazolidinones - chemistry
Oxazolidinones - pharmacology
Rats
Rats, Sprague-Dawley
Salmonella typhimurium - drug effects
Salmonella typhimurium - genetics
Structure-Activity Relationship
sulfonamide
Sulfonamides - chemistry
Sulfonamides - pharmacology
thiourea
Thiourea - chemistry
Thiourea - pharmacology
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Summary:1,3‐Oxazolidine‐2‐one is an important heterocyclic ring participating in the chemical structure of many drugs. In this research, 22 new amide/sulfonamide/thiourea derivatives (1–22) were obtained by the reaction of (S)‐4‐(4‐aminobenzyl)‐2(1H)‐1,3‐oxazolidinone with 4‐substituted benzoyl chlorides, 4‐substituted benzene sulfonyl chlorides, and 4‐substituted phenyl isothiocyanates. The structures of all synthesized compounds were clarified by FT‐IR, NMR, and mass spectroscopic and elemental analysis techniques. The synthesized compounds were screened for their antimicrobial activity. Antimicrobial susceptibility and cellular physiology were evaluated using the microbroth dilution assay and the flow cytometry method. As a result, it was determined that compound 16 displayed better antimicrobial activity than chloramphenicol against Gram‐positive bacteria, especially Staphylococcus aureus. In order to understand the mechanism of effect of the compounds on the cell membrane, fluorescence microscopy was used. Cell membrane damage of the Gram positive bacteria treated with compound 16 was observed as a result of intense staining with propidium iodide. In addition, genotoxicity, cytotoxicity, and absorption, distribution, metabolism, and excretion (ADME) parameters of compound 16 were examined and it was found as non‐mutagenic and non‐cytotoxic at the concentration at which it showed antimicrobial activity. According to the calculated ADME parameters and drug likeness scores, the compounds can be good drug candidates, especially compound 16. Twenty‐two novel amide/sulfonamide/thiourea derivatives were synthesized and tested for antimicrobial activity. (S)‐1‐(4‐Bromophenyl)‐3‐(4‐((2‐oxooxazolidin‐4‐yl)methyl)phenyl)thiourea 16 displayed better activity than chloramphenicol against Gram‐positive bacteria, especially Staphylococcus aureus. The genotoxicity, cytotoxicity, and ADME parameters of the new compounds are reported.
ISSN:0365-6233
1521-4184
DOI:10.1002/ardp.201800057