• YAKHAK HOEJI
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• v.52 no.4
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• pp.306-310
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• 2008

In vitro ${\beta}-lactamase$ inhibitory activity of 6-benzothiazole penicillins (1, 2, 3 and 4) was compared with clavulanic acid, sulbactam and tazobactam. The inhibitory activity of exomethylene compounds (3 and 4) was stronger than those of non-exomethylene compounds (1 and 2). The sulfide 3 showed stronger inhibitory activity than sulbactam, clavulanic acid andsimilar to tazobactam against ${\beta}-lactamase$ Type I enzymes. The inhibitory activity of 4 was stronger than those of sulbactam, clavulanic acid and tazobactam against Type III and IV enzymes. The in vitro antimicrobial activity of ampicillin or cefoperazone combined with 3 or 4 was stronger than those of ampicillin or cefoperazone alone against many ${\beta}-lactamase$ producing strains to show that compounds 3 and 4 have some synergistic effect. The synergistic activity of 3 and 4 was comparable to sulbactam in some ${\beta}-lactamase$ producing strains, but it was inferior to tazobactam.

• Biomolecules & Therapeutics
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• v.14 no.4
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• pp.220-225
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• 2006

Derivatives of penicillanic acid sulfones are known to be irreversible inhibitors of $\beta$-lactamase. Eight 6-tricyclic methylene penicillanic acid sulfones were prepared, and their $\beta$-lactamase inhibitory activities were evaluated against $\beta$-lactamase types I, II, III and IV. Among the tricycles attached to 6-exomethylenepenam sulfones, thiazolobenzimidazole(12a-12b), fluorene(12c), and carbazole(12e), showed inhibitory activity on type I, II and III $\beta$-lactamase. But phenanthrene(12d), and anthracene(12f-12h) derivatives showed little $\beta$-lactamase inhibitory activity. The synergic effects of the selected compound(l2b) in 1:4 combination with piperacillin showed some protection to piperacillin for the resistant strains of E. coli DC2 and P. aeruginosa 1771.

• YAKHAK HOEJI
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• v.46 no.6
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• pp.387-391
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• 2002

In vitro $\beta$-lactamase inhibitory activity of 6-exomethylene sulbactam compounds (CH-120, 130, 140, 145, 150, 155) was compared with clavulanic acid, sulbactam and tazobactam. The inhibitory activity of CH-140 was stronger than sulbactam and clavulanic acid against Type II, III, IV, TEM enzymes and stronger than tazobactam against Type IV enzyme. The inhibitory activity of CH-145 was stronger than sulbactam and clavulanic acid against Type I, II, III, IV, TEM enzymes and stronger than tazobactam against Type III, IV enzymes. The in vitro antimicrobial activity of CH-140 and CH-145 combined with piperacillin and ceftriaxone was compared with the sulbactam and tazobactam against $\beta$-lactamase producing 31 strains. But, synergistic activity of CH-140 and CH-145 was inferior to tazobactam.

• YAKHAK HOEJI
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• v.43 no.6
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• pp.782-788
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• 1999

7-Oxocephalosporanate 1 was treated with phosphonium salts 2~4 by Wittig reaction to afford 7-exomethylene cephalosporanates 5~7. They were oxidized to sulfones 8~10 with mCPBA. Deprotecton of benzhydryl 7-exomethylene cephalosporanate with $AlCl_3$ and NaHCO_3$ gave sodium salts of 7-exomethylene cephalosporanates 11~16. The ${\beta}-lactamase$ inhibitory activity of synthesized compounds 11~16 were compared with sulbactam, tazobactam and clavulanic acid against Type I, II, III, IV and TEM-2 $\beta$-lactamase in vitro. Compound 15 showed more potent activity than sulbactam and clavulanic acid against Type III, IV ${\beta}-lactamase$ enzyme.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.44-53
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• 1999

The resistant strains due to the extended-spectrum $\beta$-lactamase (ESBL) were susceptible to cefatrizine combined with clavulanic acid. The purpose of this study was to evaluate the in vitro and in vivo antibacterial activities of cefatrizine/clavulanic acid (CTRZ/CV) combination at a ratio of 2 : 1 in comparison with cefaclor (CCLO), cefuroxime (CRXM), cefuroxime axetil (CRXMA) and amoxicillin/clavulanic acid (AMXCCV). CTRZ/CV showed good activity against laboratory strains of gram-positive and gram-negative bacteria and exhibited excellent antibacterial activity against $\beta$-lactamase-producing strains. The bactericidal activity of CTRZ/CV was superior to that of CCLO and CRXM, and almost equal to that of AMXCCV against the $\beta$-lactamase-producing strains. The in vitro results were substantiated. by in vivo mouse experimental infection studies with $\beta$-lactamase-producing and non-producing strains. In mixed experimental infection due to $\beta$-lactamase-producing and non-producing strains, the therapeutic efficacy of CTRZ/CV was superior to that of CTRZ, CCLO, CRXMA and AMXCCV. In respiratory tract infection in mice due to Klebsiella pneumoniae EB4O, CTRZ/CV was more erective than CCLO, CRXMA and AMXCCV and also more efficacious than CCLO, CRXMA and AMXCCV in urinary tract infection in mice due to Escherichia coli EB13. These results indicate that CTRZ/CV is a useful drug for the treatment of infection caused by $\beta$-1actamase-producing strains including ESBL-producing strains.

• YAKHAK HOEJI
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• v.47 no.6
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• pp.456-460
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• 2003

In vitro $\beta$-lactamase inhibitory activity of 6-exomethylenepenam compounds ( 1, 2, 3, 4 and 5) was compared with clavulanic acid, sulbactam and tazobactam. The inhibitory activity of compound 3 was stronger than those of sulbactam and clavulanic acid against Type I and II enzymes and stronger than tazobactam against Type III, IV, TEM enzymes. The inhibitory activity of 5 was stronger than sulbactam and clavulanic acid against Type I and II enzymes and stronger than tazobactam against Type III, and IV enzymes. The in vitro antimicrobial activity of 3, 4 and 5 combined with ampicillin and cefoperazone was compared with the sulbactam against $\beta$-lactamase producing 27 strains. But, synergistic activity of 3 and 5 was inferior to tazobactam.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.72-72
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• 1997

합성한 5종의 6-Exomethylene penamsulfone 유도체의 Type I, Type II, Type III, TypeIV, TEM 효소에 대한 $\beta$-lactamase저해효과를 spectrophotometric assay방법으로 측정하였다. 또한 여기서 우수한 효소억제활성을 보여준 3종의 화합물을 가지고 In vitro antibacterial activity를 Agar dilution method법으로 27종의 $\beta$-lactamase생성균주에 대하여, Sulbactam, Ampicillin 및 Cefoperazone과 병용투여하여 MIC를 측정하였다.

• Korean Journal of Veterinary Research
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• v.25 no.1
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• pp.61-67
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• 1985

One hundred and twenty seven strains of Gram-negative rods (72 E. coli, 45 Klebsieila pneumoniae, 8 Enterobacter spp. and 2 Pseudomonas aeruginosa) isolated from bovine mastitis were examined for resistance to ampicilin, carbenicillin and cefazolin, ${\beta}$-lactamase activity and transferable ${\beta}$-lactamase plasmids. Stains resistant to ampicillin were 13.9% in E. coli, 93.3% in Klebsiella pneumoniae, 87.5% in Enterobacter. spp. and all in Pseudomonas aeruginosa, Resistance of E. coli, Klebsiella pneumoniae and Enterobacter spp. to ampicillin was due to the ${\beta}$-lactamases, but all Pseudomonas aeruginosa exhibited a high level of the non-enzymic resistance. Transferable plasmid-mediated ${\beta}$-lactamase synthesis was demonstrated in 61.9% of Klebsiella pneumoniae, 50% of E. coli and 42.9% of Enterobacter spp. The same ${\beta}$-lactamase plasmids specified different resistance levels to various ${\beta}$-lactam antibiotics in different recipients.

• Korean Journal of Veterinary Research
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• v.43 no.1
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• pp.113-120
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• 2003

The antimicrobial effect of ${\beta}$-lactam antibiotics, which had ${\beta}$-lactamase inhibitor activity, on Staphylococcus aureus isolated from mastitis was investigated in this study. Out of 166 isolates, 99 isolates (59.6%) produced ${\beta}$-lactamase, and 98 isolates of 99 were ${\beta}$-lactamase positive in above $12.5{\mu}g/m{\ell}$ MIC of penicillin. In the providence distribution, ${\beta}$-lactamase production rate of 4 providence, Gangwon, Gyeonggi, Chungcheong, and Jeolla was 100%, 65.7%, 58.8%, and 50.0%, respectively. Antibiotic activities of ${\beta}$-lactam antibiotics against lactamase positive isolates also were investigated. Antimicrobial effects of ampicillin/sulbactam or amoxicillin/clavulanic acid treated group were better than ampicillin or amoxicillin treated group. In antimicrobial effects on intracellular S aureus, there was no difference 1 hour and 4 hour treatment in control, ampicillin, and amoxicillin group, but in 18 hours treatment, ampicillin/sulbactam or amoxicillin/clavulanic acid had a better effect than ampicillin or amoxicillin (p<0.05).

• Journal of the Korean Chemical Society
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• v.49 no.5
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• pp.461-469
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• 2005