KB-5246
目录号 : GC32334
KB-5246是一种四环喹诺酮，具有抗菌活性。
Cas No.:119474-55-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Bactericidal activity is tested by evaluating the reduction of viable cells during exposure to KB-5246 for 24 h. An overnight culture of microorganisms in sensitivity test broth is diluted to about 104 CFU/mL in the same medium and incubated at 37°C on a shaker. After 2 h of incubation, KB-5246 is added to the cultures at final concentrations of one half, one, two, or four times the MIC[1]. |
Animal experiment: | In vivo antibacterial activity against systemic infections in mice is determined. Ten male ddY mice weighing 19 to 23 g each are used for each dose level. An overnight culture in brain heart infusion broth at 37°C is diluted appropriately in the same medium with 4% gastrin mucin. A 0.2 mL sample of a bacterial suspension, corresponding to a dose 1 to 25 times higher than the minimal lethal dose, is injected intraperitoneally. Immediately after infection, mice are treated orally with a single dose of KB-5246. The number of mice surviving at each dose is counted 7 days after infection. The 50% effective dose is calculated by the probit method[1]. |
References: [1]. Kotera Y, et al. In vitro and in vivo antibacterial activities of KB-5246, a new tetracyclic quinolone. Antimicrob Agents Chemother. 1989 Nov;33(11):1896-900. | |
KB-5246 is a tetracyclic quinolone and displays antibacterial activities.
KB-5246 is a tetracyclic quinolone and displays antibacterial activities. The MICs for 90% of isolates tested (MIC90s) of KB-5246 against gram-positive microorganisms such as Staphylococcus aureus, including methicillin-resistant S. aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Streptococcus pyogenes, are 0.39 μg/mL. KB5246 inhibits 90% of isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca at a concentration of 0.10 μg/mL or less. When a concentration of KB-5246 at the MIC or higher is added, no regrowth after 24 h of incubation is observed[1].
The 50% effective dose values of KB-5246 against S. pneumoniae 2132 infections are 50.5 mg/kg of body weight. The activities of KB-5246 against S. aureus Smith, P. aeruginosa GN11189, and Serratia marcescens GN7577 infections are comparable to those of ofloxacin and greater than those of norfloxacin[1].
[1]. Kotera Y, et al. In vitro and in vivo antibacterial activities of KB-5246, a new tetracyclic quinolone. Antimicrob Agents Chemother. 1989 Nov;33(11):1896-900.
| Cas No. | 119474-55-4 | SDF | |
| Canonical SMILES | [H]Cl.CN1CCN(C2=C(F)C=C3C4=C2OCC5=CSC(N45)=C(C(O)=O)C3=O)CC1 | ||
| 分子式 | C18H17ClFN3O4S | 分子量 | 425.86 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3482 mL | 11.7409 mL | 23.4819 mL |
| 5 mM | 0.4696 mL | 2.3482 mL | 4.6964 mL |
| 10 mM | 0.2348 mL | 1.1741 mL | 2.3482 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Activity of KB-5246 against outer membrane mutants of Escherichia coli and Salmonella typhimurium
Antimicrob Agents Chemother 1990 Jul;34(7):1323-5.PMID:2167038DOI:10.1128/AAC.34.7.1323.
The inhibitory activity of KB-5246 against Escherichia coli DNA gyrase and the antibacterial activity and apparent uptake in E. coli and Salmonella typhimurium outer membrane mutants of KB-5246 were measured. The 50% inhibitory concentrations of KB-5246, ciprofloxacin, oflaxacin, and norfloxacin for E. coli KL-16 DNA gyrase were 0.72, 0.62, 0.84, and 1.16 micrograms/ml, respectively. The activity of KB-5246 was twofold lower against an OmpF-deficient mutant and twofold higher against a mutant which produced OmpF constitutively than against the parent with osmoregulated OmpF production. KB-5246 had twofold-higher activity against a deep rough mutant of S. typhimurium than against the parent. The apparent uptake of KB-5246 in the OmpF-deficient mutant was decreased and its uptake in the deep rough mutant was increased when compared with those in the parents. These results suggest that KB-5246 is taken up by porin and nonporin pathways and has strong inhibitory activity against DNA gyrase, resulting in potent antibacterial activity.
In vitro and in vivo antibacterial activities of KB-5246, a new tetracyclic quinolone
Antimicrob Agents Chemother 1989 Nov;33(11):1896-900.PMID:2610501DOI:10.1128/AAC.33.11.1896.
The in vitro and in vivo antibacterial activities of KB-5246, a tetracyclic quinolone, were compared with those of ciprofloxacin, ofloxacin, and norfloxacin. KB-5246 demonstrated a broad antibacterial spectrum. The in vitro activity of KB-5246 against gram-negative bacteria was higher than that of ofloxacin or norfloxacin and was comparable to that of ciprofloxacin. KB-5246 demonstrated the greatest activity against gram-positive bacteria of the four agents tested. Among Streptococcus pyogenes strains resistant to 1.56 micrograms of norfloxacin per ml, there were 26 strains susceptible to 0.2 micrograms of KB-5246 per ml. Similarly, among the Staphylococcus aureus and Staphylococcus epidermidis strains resistant to 3.13 micrograms of norfloxacin per ml, there were 23 S. aureus and 11 S. epidermidis strains susceptible to 0.39 micrograms of KB-5246 per ml. Among the Streptococcus pneumoniae and Enterococcus faecalis strains resistant to 12.5 micrograms of norfloxacin per ml, there were 5 S. pneumoniae and 10 E. faecalis strains susceptible to 0.39 micrograms of KB-5246 per ml. KB-5246 had bactericidal activity at the MIC. KB-5246 demonstrated excellent antibacterial activity against various systemic infections in mice. After oral administration, KB-5246 was as active as ofloxacin and about two times more active than norfloxacin.
Lack of effect of carbonyl cyanide m-chlorophenylhydrazone on KB-5246 accumulation by Staphylococcus aureus
Antimicrob Agents Chemother 1992 Apr;36(4):883-5.PMID:1323957DOI:10.1128/AAC.36.4.883.
The accumulation of KB-5246 in a quinolone-susceptible strain of Staphylococcus aureus was about 70 times that of norfloxacin. Carbonyl cyanide m-chlorophenylhydrazone increased the accumulation of norfloxacin about eightfold, but it did not influence that of KB-5246. The low efflux of KB-5246 from S. aureus may contribute to its potent antibacterial activity.
In vitro properties of the newer quinolones
Prog Drug Res 1992;38:19-28.PMID:1609115doi
Table 5 summarizes the activity of the newer quinolones against various bacteria including intracellular bacteria and the other microorganisms. In this table, the overall MIC ranges of NFLX, ENX, OFLX, and CPFX, for susceptible isolates of each bacteria are schematically presented. The newer quinolones are considered to have sufficient activity against gram-negative enteric bacteria, N. gonorrhoeae, and H. influenzae and Legionella spp. Since OFLX and CPFX show only moderate activity against staphylococci, streptococci, and P. aeruginosa, improvement is expected. As shown in Table 3, TFLX and the recent investigational quinolones such as SPFX and KB-5246 show higher and promising activity against gram-positive bacteria. However, further studies are needed with longer periods to indicate whether these newer agents will be able to stop the increase of quinolone-resistant staphylococci. Furthermore, the activity of the newer quinolones against obligate anaerobes such as clostridia and bacteroides are considered to be insufficient for clinical use. Whether it will be possible to synthesize quinolones with anti-anaerobic activity sufficiently for clinical treatment is uncertain. Although Mycobacterium tuberculosis is susceptible to the newer quinolones, other mycobacteria are somewhat less susceptible to this class of agents. In addition, the newer quinolones have adequate activity against mycoplasma, chlamydia and rickettsia. From a microbiological viewpoint the prospects for the newer quinolones would be primarily to find agents that have higher anti-staphylococcal and anti-streptococcal activity. Secondly, agents possessing superior activity against obligate anaerobes such as Bacteroides spp. and Clostridium spp. are expected to synthesize. Furthermore, it may be possible to synthesize compounds that are sufficiently active for clinical use against atypical mycoplasma, chlamydia, and rickettsia.
Structure-activity relationship of quinolone antibacterial agents: the effects of C-2 substitution
Drugs Exp Clin Res 1990;16(5):215-24.PMID:1964116doi
Very little is known about the structure-activity relationship of quinolone antibacterials at the 2-position. Because of the loss of biological activity with 2-methyl and 2-hydroxyl substitution, modifications at C-2 were generally considered to be unfavourable. Quinolone derivatives having a ring between positions 1 and 2 were recently shown to have biological activity. The sulfur-bridged analogs such as the benzothiazolo[3,2-a]quinolone, KB-5246 and NAD-394 have been reported to be highly active in vitro. The authors have synthesized 2-methylthiociprofloxacin, 2-methylofloxacin, the 5-oxopyrrolo[1,2-a]quinoline and isothiazolonaphthyridine to assess the importance of the sulfur atom on biological activity as well as the effect of C-2 substituent on the spatial arrangements of N-1 or the 3-carboxylic group. It was found that the planarity between the 4-keto and 3-carboxylic acid groups of quinoline molecules is the most important criterion for biological activity. The syntheses of the above four compounds are also described.