17796-70-2Relevant academic research and scientific papers
Allicin-inspired thiolated fluoroquinolones as antibacterials against ESKAPE pathogens
Sheppard, Jordan G.,Long, Timothy E.
, p. 5545 - 5549 (2016)
Thiolated fluoroquinolones were synthesized from ciprofloxacin and evaluated for antimicrobial activity against a panel of pathogenic bacteria. Gram-positive species including methicillin-resistant Staphylococcus aureus (MRSA) exhibited the highest level of increased sensitivity toward ciprofloxacin bound with a N-propylthio substituent. Evidence was found that the antibiotics form disulfides with low molecular weight thiols in bacteria and potentiate generation of cytosolic reactive oxygen species (ROS). In final analysis, the enhanced anti-MRSA activity of thiolated fluoroquinolones was attributed to increased cell permeability and reaction with cytosolic thiols that yields an inactive disulfide metabolite and the parent drug ciprofloxacin as an inhibitor of DNA synthesis.
Copper-Catalyzed Electrophilic Thiolation of Organozinc Halides by Using N-Thiophthalimides Leading to Polyfunctional Thioethers
Gra?l, Simon,Hamze, Clémence,Koller, Thadd?us J.,Knochel, Paul
supporting information, p. 3752 - 3755 (2019/02/13)
(Hetero)aryl, benzylic, and alkyl zinc halides were thiolated with N-thiophthalimides at 25 °C within 1 h in the presence of 5–10 % Cu(OAc)2?H2O to furnish the corresponding polyfunctionalized thioethers in good yields. This electrop
Preparation of sulfenyl pyrroles
Gillis, H. Martin,Greene, Lana,Thompson, Alison
experimental part, p. 112 - 116 (2009/06/18)
Sulfenyl groups are attracting interest as masking/protecting groups for pyrroles. A facile one-step synthesis of sulfenyl pyrroles, involving the reaction of pyrroles with N-(aryl- and alkylthio)phthalimides in the presence of MgBr2, is reported and the methodology extends to include sulfinyl pyrroles. The one-step procedure gives good yields and is more efficient and practical than current multistep protocols to sulfenyl pyrroles that involve thiocyanato pyrrolic intermediates. A convenient procedure for the synthesis of N-(aryl- and alkylthio)phthalimides is also reported. Georg Thieme Verlag Stuttgart.
N-Thiolated β-lactam antibacterials: Effects of the N-organothio substituent on anti-MRSA activity
Heldreth, Bart,Long, Timothy E.,Jang, Seyoung,Reddy, G. Suresh Kumar,Turos, Edward,Dickey, Sonja,Lim, Daniel V.
, p. 3775 - 3784 (2007/10/03)
A study on the structure-activity profiles of N-thiolated β-lactams 1 is reported which demonstrates the importance of the N-organothio moiety on antibacterial activity. Our results indicate that elongation of the N-alkylthio residue beyond two carbons, or extensive branching within the organothio substituent, diminishes antibacterial effects. Of the derivatives we examined, the N-sec-butylthio β-lactam derivative 5g possesses the strongest growth inhibitory activity against methicillin-resistant Staphylococcus aureus strains. Sulfur oxidation state is important, as the N-sulfenyl and N-sulfinyl groups provide for the best antibacterial activity, while lactams bearing the N-sulfonyl or N-sulfonic acid functionalities have much weaker or no anti-MRSA properties. Stereochemistry within the organothio chain does not seem to be a significant factor, although for N-sec-butylthio β-lactams 15a-d, the 3R,4S-lactams 15c, d are more active than the 3S,4R-stereoisomers 15a, b in agar diffusion experiments. The N-methylthio lactams are the most sensitive to the presence of glutathione, followed by N-ethylthio and N-sec-butylthio lactams, which indicates that bioactivity and perhaps bacterial selectivity of the lactams may be related to the amount of organothiols in the bacterial cell. These results support the empirical model for the mechanism of action of the compounds in which the lactam transverses the bacterial membrane to deliver the organothio moiety to its cellular target.
