Potent DNA gyrase inhibitors; novel 5-vinylpyrazole analogues with Gram-positive antibacterial activity

2004 ◽  
Vol 14 (11) ◽  
pp. 2863-2866 ◽  
Author(s):  
Akihiko Tanitame ◽  
Yoshihiro Oyamada ◽  
Keiko Ofuji ◽  
Kenji Suzuki ◽  
Hideaki Ito ◽  
...  
ChemInform ◽  
2004 ◽  
Vol 35 (38) ◽  
Author(s):  
Akihiko Tanitame ◽  
Yoshihiro Oyamada ◽  
Keiko Ofuji ◽  
Kenji Suzuki ◽  
Hideaki Ito ◽  
...  

2005 ◽  
Vol 15 (19) ◽  
pp. 4299-4303 ◽  
Author(s):  
Akihiko Tanitame ◽  
Yoshihiro Oyamada ◽  
Keiko Ofuji ◽  
Hideo Terauchi ◽  
Motoji Kawasaki ◽  
...  

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e69751 ◽  
Author(s):  
Juan Sun ◽  
Peng-Cheng Lv ◽  
Yong Yin ◽  
Rong-Ju Yuan ◽  
Jian Ma ◽  
...  

2014 ◽  
Vol 12 (6) ◽  
pp. 998 ◽  
Author(s):  
Jia-Jia Liu ◽  
Juan Sun ◽  
Yun-Bin Fang ◽  
Yong-An Yang ◽  
Rui-Hua Jiao ◽  
...  

2014 ◽  
Vol 59 (1) ◽  
pp. 467-474 ◽  
Author(s):  
Michael D. Huband ◽  
Patricia A. Bradford ◽  
Linda G. Otterson ◽  
Gregory S. Basarab ◽  
Amy C. Kutschke ◽  
...  

ABSTRACTAZD0914 is a new spiropyrimidinetrione bacterial DNA gyrase/topoisomerase inhibitor with potentin vitroantibacterial activity against key Gram-positive (Staphylococcus aureus,Staphylococcus epidermidis,Streptococcus pneumoniae,Streptococcus pyogenes, andStreptococcus agalactiae), fastidious Gram-negative (Haemophilus influenzaeandNeisseria gonorrhoeae), atypical (Legionella pneumophila), and anaerobic (Clostridium difficile) bacterial species, including isolates with known resistance to fluoroquinolones. AZD0914 works via inhibition of DNA biosynthesis and accumulation of double-strand cleavages; this mechanism of inhibition differs from those of other marketed antibacterial compounds. AZD0914 stabilizes and arrests the cleaved covalent complex of gyrase with double-strand broken DNA under permissive conditions and thus blocks religation of the double-strand cleaved DNA to form fused circular DNA. Whereas this mechanism is similar to that seen with fluoroquinolones, it is mechanistically distinct. AZD0914 exhibited low frequencies of spontaneous resistance inS. aureus, and if mutants were obtained, the mutations mapped togyrB. Additionally, no cross-resistance was observed for AZD0914 against recent bacterial clinical isolates demonstrating resistance to fluoroquinolones or other drug classes, including macrolides, β-lactams, glycopeptides, and oxazolidinones. AZD0914 was bactericidal in both minimum bactericidal concentration andin vitrotime-kill studies. Inin vitrocheckerboard/synergy testing with 17 comparator antibacterials, only additivity/indifference was observed. The potentin vitroantibacterial activity (including activity against fluoroquinolone-resistant isolates), low frequency of resistance, lack of cross-resistance, and bactericidal activity of AZD0914 support its continued development.


2004 ◽  
Vol 12 (21) ◽  
pp. 5515-5524 ◽  
Author(s):  
Akihiko Tanitame ◽  
Yoshihiro Oyamada ◽  
Keiko Ofuji ◽  
Mika Fujimoto ◽  
Kenji Suzuki ◽  
...  

2021 ◽  
Vol 14 (5) ◽  
pp. 399
Author(s):  
Lamya H. Al-Wahaibi ◽  
Amer A. Amer ◽  
Adel A. Marzouk ◽  
Hesham A.M. Gomaa ◽  
Bahaa G. M. Youssif ◽  
...  

A novel series of ciprofloxacin hybrids comprising various heterocycle derivatives has been synthesized and structurally elucidated using 1H NMR, 13C NMR, and elementary analyses. Using ciprofloxacin as a reference, compounds 1–21 were screened in vitro against Gram-positive bacterial strains such as Staphylococcus aureus and Bacillus subtilis and Gram-negative strains such as Escherichia coli and Pseudomonas aeruginosa. As a result, many of the compounds examined had antibacterial activity equivalent to ciprofloxacin against test bacteria. Compounds 2–6, oxadiazole derivatives, were found to have antibacterial activity that was 88 to 120% that of ciprofloxacin against Gram-positive and Gram-negative bacteria. The findings showed that none of the compounds tested had antifungal activity against Aspergillus flavus, but did have poor activity against Candida albicans, ranging from 23% to 33% of fluconazole, with compound 3 being the most active (33% of fluconazole). The most potent compounds, 3, 4, 5, and 6, displayed an IC50 of 86, 42, 92, and 180 nM against E. coli DNA gyrase, respectively (novobiocin, IC50 = 170 nM). Compounds 4, 5, and 6 showed IC50 values (1.47, 6.80, and 8.92 µM, respectively) against E. coli topo IV in comparison to novobiocin (IC50 = 11 µM).


2004 ◽  
Vol 47 (14) ◽  
pp. 3693-3696 ◽  
Author(s):  
Akihiko Tanitame ◽  
Yoshihiro Oyamada ◽  
Keiko Ofuji ◽  
Mika Fujimoto ◽  
Noritaka Iwai ◽  
...  

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