TY - JOUR
T1 - Comparative study of the inhibition of metallo-β-lactamases (IMP-1 and VIM-2) by thiol compounds that contain a hydrophobic group
AU - Jin, Wanchun
AU - Arakawa, Yoshichika
AU - Yasuzawa, Hisami
AU - Taki, Tomoko
AU - Hashiguchi, Ryo
AU - Mitsutani, Kana
AU - Shoga, Asumi
AU - Yamaguchi, Yoshihiro
AU - Kurosaki, Hiromasa
AU - Shibata, Naohiro
AU - Ohta, Michio
AU - Goto, Masafumi
PY - 2004/6
Y1 - 2004/6
N2 - For the purpose of screening of inhibitors that are effective for wide range of metallo-β-lactamases, the inhibitory effect of two series of compounds, 2-ω-phenylalkyl-3-mercaptopropionic acid (PhenylCnSH (n=1-4)) and N-[(7-chloro-quinolin-4-ylamino)-alkyl]-3-mercapto-propionamide (QuinolineCnSH (n=2-6)), where n denotes the alkyl chain length, on metallo-β-lactamases IMP-1 and VIM-2 was examined. These inhibitors contain a thiol group and a hydrophobic group linked by variable-length methylene chain. PhenylCnSH (n=1-4) was found to be a potent inhibitor of both IMP-1 and VIM-2. PhenylC4SH was the potent inhibitor of both IMP-1 (IC50=1.2 μM) and VIM-2 (IC50=1.1 μM) among this study. When the number of methylene units was varied, QuinolineC4SH showed the maximum inhibitory activity against IMP-1 and VIM-2 (IC50=2.5 μM and IC 50=2.4 μM). The relationship between the inhibitory effect of the alkyl chain length was different for both series of inhibitors, suggesting that IMP-1 has a tighter binding site than VIM-2. QuinolineCnSH did not serve as a fluorescence reagent for metallo-β-lactamases.
AB - For the purpose of screening of inhibitors that are effective for wide range of metallo-β-lactamases, the inhibitory effect of two series of compounds, 2-ω-phenylalkyl-3-mercaptopropionic acid (PhenylCnSH (n=1-4)) and N-[(7-chloro-quinolin-4-ylamino)-alkyl]-3-mercapto-propionamide (QuinolineCnSH (n=2-6)), where n denotes the alkyl chain length, on metallo-β-lactamases IMP-1 and VIM-2 was examined. These inhibitors contain a thiol group and a hydrophobic group linked by variable-length methylene chain. PhenylCnSH (n=1-4) was found to be a potent inhibitor of both IMP-1 and VIM-2. PhenylC4SH was the potent inhibitor of both IMP-1 (IC50=1.2 μM) and VIM-2 (IC50=1.1 μM) among this study. When the number of methylene units was varied, QuinolineC4SH showed the maximum inhibitory activity against IMP-1 and VIM-2 (IC50=2.5 μM and IC 50=2.4 μM). The relationship between the inhibitory effect of the alkyl chain length was different for both series of inhibitors, suggesting that IMP-1 has a tighter binding site than VIM-2. QuinolineCnSH did not serve as a fluorescence reagent for metallo-β-lactamases.
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U2 - 10.1248/bpb.27.851
DO - 10.1248/bpb.27.851
M3 - Article
C2 - 15187432
AN - SCOPUS:16644376850
SN - 0918-6158
VL - 27
SP - 851
EP - 856
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
IS - 6
ER -