• Bulletin of the Korean Chemical Society
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• v.31 no.12
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• pp.3644-3652
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• 2010

The metallo-$\beta$-lactamases ($M{\beta}Ls$) are clinically significant enzymes which readily hydrolyze most $\beta$-lactam antibiotics. Discovering potential inhibitors for the $M{\beta}Ls$ is an expensive, time consuming endeavor. Virtual screening can sieve out inhibitor candidates with incompatible features prior to synthesis, decreasing these costs. Using Autodock 4.0, the binding locations and energies of four previously-studied potential inhibitors and four additional compounds obtained from the National Cancer Institute (NCI) database were computationally calculated. Based on the docking models of these eight compounds, we then designed several hypothetical inhibitor structures, compounds A through F, and performed their respective docking experiments. The docking results for compound F showed that it binds to the zinc containing active sites with a lowest predicted binding energy of -6.70 kcal/mol, suggesting F is the most likely potential $M{\beta}L$ inhibitor.

• 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.

• YAKHAK HOEJI
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• v.41 no.1
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• pp.126-131
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• 1997

To overcome the problems of the resistance to clavulanic acid, many researchers are developing novel inhibitors that are not sensitive to new mutant ${\beta}$-lactamases. In order to evaluate newly synthesized compound CH2150 (Sodium (3S.5R)-6(Z)-[1-{1-(2-{2-benzoxazoly}thioethyl)-l.2,3-txiazol-4-yl}methylene] penicillanate-1,1-dioxide) as a ${\beta}$-lactamase inhibitor, we examined inhibitory activity of CH2150 against ${\beta}$-lactamases of clinical isolates resistant to ampicillin/sulbactam(12 strains of Escherichia coli and 13 strains of Staphylococcus aureus), and compared with that of sulbactam. Nitrocefin was used as substrate for ${\beta}$-lactamases, and the increase of absorbance was measured spectrophotometerically at 482 nm. ${\beta}$-Lactarnase inhibition of CH2150 against ${\beta}$-lactamases was 73 ~ 96% in E. coli and 76 ~ 79% in S. aureus. Comparatively, that of sulbactam was 96 ~ 100% and 96 ~ 100%, respectively. The inhibitory activity of CH2150 was slightly lower than that of sulbactam. The MIC values of ampicillin combined with CH2150 (2:1) for the clinical isolates were 4~512 ${\mu}$g/ml for E. coli and 1.0 ~ 64 ${\mu}$g/ml for S. aureus, whereas 0.5~16 ${\mu}$g/ml for E. coli and 0.25~8 ${\mu}$g/ml for S. aureus when combined with sulbactam (2:1).

• Archives of Pharmacal Research
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• v.20 no.6
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• pp.647-651
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• 1997

The 6, 6-dibromopenam 6 was treated with $CH_{3}/MgBr$ and carbaldehyde 5 to afford the 6-bromo-6-(1-hydroxy-1-methyl)penicillanate 7, which was reacted with acetic anhybride to give acetoxy compound 8. The deacetobromination of 8 with zinc and acetic acid gave 6-exomethylenpenams, Z-isomer 9 and E-isomer 10, which were oxidized to sulfones 11 and 12 by m-CPBA. The p-methoxybenzyl compounds were deprotected by $AlCl_{3}$ and neutralized to give the sodium salts 13, 14, and 15.

• Korean Journal of Plant Resources
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• v.33 no.6
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• pp.578-585
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• 2020

This study was designed to assess the possibility of using medicinal plant extracts as β-lactamase inhibitors to control antibiotic-resistant Staphylococcus aureus. The susceptibilities of S. aureus ATCC 15564 (SA^WT), ciprofloxacininduced S. aureus ATCC 15564 (SA^CIP), oxacillin-induced S. aureus ATCC 15564 (SA^OXA), and clinically-isolated S. aureus CCARM 3008 (SA^CLI) to ampicillin were determined in the absence and presence of medicinal plant extracts, including Cleyera japonica (CJ), Carpinus laxiflora (CL), Euphorbia helioscopia (EH), Euscaphis japonica (EJ), Oenothera erythrosepala (OE), and Rosa multiflora (RM). The phenotypic change in the clear inhibition zones around ampicillin disc was observed for SA^WT, SA^CIP, and SA^OXA, indicating the production of ampicillinase. Compared to the controls, the MICs of ampicillin against SA^WT, SA^CIP, and SA^OXA were decreased from 4 to 0.5 ㎍/mL in the presence of CL, 16 to 4 ㎍/mL in the presence of RM, and 32 to 2 ㎍/mL in the presence of CL, EH, and RM, respectively. The medicinal plant extracts, OE, EJ, and CL, effectively inhibited the β-lactamase activities of SA^WT (78%), SA^CIP (57%), and SA^OXA (76%) when compared to the control. This results suggest that the medicinal plant extracts can be used as BLIs to control the antibiotic-resistant S. aureus.

• YAKHAK HOEJI
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• v.47 no.5
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• pp.288-292
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• 2003

The synthesis of new 6-exomethylene penams with substituted triazole ring was described. The 6,6-dibromopenam 5 was reacted with $CH_3$MgBr and substituted triazole 4 to afford the 6-bromo penicillanate 6, which was treated with acetic anhydride to give acetoxy compound 7. The deacetobromination of acetoxy compound 7 with zinc and acetic acid gave 6-exomethylene penams 8, which was oxidized to sulfones 9 by m-CPBA. The p-methoxybenzyl compounds 6∼9 were deprotected by AlCl$_3$ and neutralized to give the sodium salts 10∼13.

• YAKHAK HOEJI
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• v.44 no.2
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• pp.128-134
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• 2000

The synthesis of new 6-exomethylene penams with triazole ring was described. The 6,6-dibromopenam 5 was treated with $CH_3$MgBr and carbaldehyde 4 to afford the 6-bromo-6-(1-hydroxy-1-methyl)penicillanate 6, which was reacted with acetic anhydride to give acetoxy compound 7. The deacetobromination of 7 with zinc and acetic acid gave 6-exomethylenpenams, Z-isomer 8 and E-isomer 9, which were oxidized to sulfones 10 and 11 by m-CPBA. The p-methoxybenzyl compounds 6~11 were deprotected by AlCl$_3$ and neutralized to give the sodium salts 12~17.

• YAKHAK HOEJI
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• v.48 no.5
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• pp.303-308
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• 2004

The synthesis of new 6-triazole exomethylenepenams was described. The 6,6-dibromopenam 5 was reacted with $CH_3$MgBr and substituted triazole 4 to afford the 6-bromo penicillanate 6, which was treated with acetic anhydride to give acetoxy compound 7. The deacetobromination of acetoxy compound 7 with zinc and acetic acid gave 6-exomethylene penams 8 and 9, which were oxidized to sulfones 10 and 11 by m-CPBA. The p-methoxybenzyl compounds 6-11 were deprotected by AlCl$_3$ and neutralized to give the sodium salts 12-17.

• Childhood Kidney Diseases
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• v.25 no.1
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• pp.22-28
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• 2021

Purpose: The purpose of this study was to investigate the clinical outcomes of non-carbapenem treatment for urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) in young children. Methods: We retrospectively reviewed the medical records of children under 2 years of age who were diagnosed and treated for UTIs caused by ESBL-producing E. coli from September 2014 to March 2020. Results: Forty-three children under 2 years of age were treated with non-carbapenem antimicrobials for UTIs caused by ESBL-producing E. coli without bloodstream infections. The overall clinical and microbiological success rates for empirical antimicrobial treatment were 90.7% and 97.7%. Three of the patients (7.0%) experienced a relapse of UTI within a month. An in vitro susceptibility test showed that two patients were sensitive and one was resistant to the antimicrobial treatments. Furthermore, there were no significant differences in the time to defervescence, clinical success, microbiological success, and relapse rate between the susceptible (n=13) and non-susceptible groups (n=30). Conclusion: In this study, the overall relapse rate of patients treated with non-carbapenem antimicrobials was 7.0%. The patients showed high success rates in the clinical and microbiological responses to the non-carbapenems regardless of the results of the in vitro antimicrobial susceptibility test. These results provide evidence that non-carbapenems may be viable alternative treatments for UTIs caused by ESBL-producing E. coli.

• YAKHAK HOEJI
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• v.46 no.6
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• pp.381-386
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• 2002

The synthesis of new 6-exomethylene sulbactam derivatives with 5-methyl-1,3,4-thiadiazole was described. The 6,6-dibromopenam 5 was reacted with $CH_3$MgBr and carbaldehyde 4 to afford the 6-bromo-6-(1-hydroxy-1-methyl)penicillanate 6, which was treated with acetic anhydride to give acetoxy compound 7. The deacetobromination of acetoxy compound 7 with zinc and acetic acid gave 6-exomethylen penams, Z-isomer 8 and E-isomer 9, which was oxidized to sulfones 10 by m-CPBA. The p-methoxybenzyl compounds 6-10 were deprotected by AlCl$_3$ and neutralized with NaOH solution to give the sodium salts 11-15.