3048
L. Ouyang et al. / Bioorg. Med. Chem. Lett. 22 (2012) 3044–3049
Figure 4. Compound 8t docked in the active site of S. aureus methionyl-tRNA synthetase. (a) Residues involved in interaction with the ligand. (b) The protein molecule is
shown in the surface representation, whereas docked compounds are illustrated in the stick representation
6. Haydon, D. J.; Stokes, N. R.; Ure, R.; Galbraith, G.; Bennett, J. M.; Brown, D. R.;
standard drug Ampicillin and Cefotaxime displayed better activity
on the non-resistant bacteria. Impressively, the new compound 8t
Baker, P. J.; Barynin, V. V.; Rice, D. W.; Sedelnikova, S. E.; Heal, J. R.; Sheridan, J.
M.; Aiwale, S. T.; Chauhan, P. K.; Srivastava, A.; Taneja, A.; Collins, I.; Errington,
seems to be more potential on drug-resistant bacteria especially
methicillin-resistant S. aureus and vancomycin-resistant E. faecalis.
From the results of molecular docking, we speculated that com-
pound 8t might be a new MetRS inhibitor. Importantly, our study
provided an effective entry for the synthesis of a new small mole-
cule and a good lead for subsequent optimization used as antibac-
terial agents. The preliminary results seem to be very promising
and we are continuing to develop more suitable methods for the
comprehensive evaluation of methionyl-tRNA enzyme inhibitory
activity and in vivo animal models.
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Acknowledgments
We wish to thank Professor Xiaokang Liu and Dr. Xiaoli Ji
(Sichuan University) for providing an assessment of pharmacologi-
cal test for all the compounds in this program. We also thank
Dr. Huailong Xu (Sichuan University) for good suggestions on
homology modeling and molecular docking. Financial support
from National Natural Science Foundation of China (Nos.
81102325 and 81001357), China Postdoctoral Science Foundation
(No. 20110491729) and Youth Foundation of Sichuan University
(No. 2010SCU11067) is gratefully acknowledged.
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Antimicrob. Agents Chemother. 2005, 49, 4253.
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Supplementary data
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