Abstract
Two series of novel 2-butyl succinate-based Hydroxamate derivatives containing isoxazole rings were synthesized, characterized and evaluated for antibacterial activity. The synthesized compounds were found to exhibit weak to moderate inhibitory activity against Staphytlococcus aureu and Klebsiellar pneumonia in vitro. All the compounds synthesized were found to be more effective against Klebsiellar pneumonia compared to Staphytlococcus aureu.
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Aarons, S. J., Sutherland, I. W., Chakrabarty, A. M., and Gallagher, M. P., A novel gene, algK, from the alginate biosynthetic cluster of Pseudomonas aeruginosa. Microbiology, 143, 641–652 (1997).
Broughton, B. J., Chaplen, P., Freeman, W. A., Warren, P. J., Wooldridge, K. R. H., and Wright, D. E., Studies concerning the antibiotic actinonin. Part VIII. Structureactivity relationships in the actinonin series. J. Chem. Soc. Perkin Trans. I, 857–860 (1975).
Chen, D. Z., Patel, D. V., Hackbarth, C. J., Wang, W., Dreyer, G., Young, D. C., Margolis, P. S., Wu, C., Ni, Z., Trias, J., White, R. J., and Yuan, Z., Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor. Biochemistry, 39, 1256–1262 (2000).
Chen, D., Hackbarth, C., Ni, Z. J., Wu, C., Wang, W., Jain, R., He, Y., Bracken, K., Weidmann, B., Patel, D. V., Trias, J., White, R. J., and Yuan, Z., Peptide deformylase inhibitors as antibacterial agents: Identification of VRC3375, a proline-3-alkylsuccinyl hydroxamate derivative, by using an integrated combinatorial and medicinal chemistry approach. Antimicrob. Agents Chemother., 48, 250–261 (2004).
Chu, M., Mierzwa, R., He, L., Xu, L., Gentile, F., Terracciano, J., Patel, M., Miesel, L., Bohanon, S., Kravec, C., Cramer, C., Fischman, T. O., Hruza, A., Ramanathan, L., Shipkova, P., and Chan, T., Isolation and structure elucidation of two novel deformylase inhibitors produced by Streptomyces sp. Tetrahedron Lett., 42, 3549–3551 (2001).
Chung, Y. J., Kim, D., Choi, K. Y., Kim, B. H., Synthesis and inhibitory activities of HIV-1 protease inhibitors containing 2-isoxazoline derivatives. Korean J. Med. Chem., 5, 141–161 (1995).
Clements, J. M., Beckett, P., Brown, A., Catlin, G., Lobell, M., Palan, S., Thomas, W., Whittaker, M., Baker, P. J., Rodgers, F., Barynin, V., Rice, D. W., Hunter, M. G., Antibiotic Activity and Characterization of BB-3497, a Novel Peptide Deformylase Inhibitor. Antimicrob. Agents Chemother., 45, 563–570 (2001).
Davies, J., Inactivation of antibiotics and the dissemination of resistance genes. Science, 264, 375–382 (1994).
East, S. P., Beckett, R. P., Brookings, D. C., Clements, J. M., Doel, S., Keavey, K., Pain, G., Smith, H. K., Thomas, W., Thompson, A. J., Todd, R. S., and Whittaker, M., Peptide deformylase inhibitors with activity against respiratory tract pathogens. Bioorg. Med. Chem. Lett., 14, 59–62 (2004).
Giglione, C., Serero, A., and Pierre, M., Identification of eukaryotic peptide deformylases reveals universality of Nterminal protein processing mechanisms. EMBO J., 19, 5916–5929 (2000).
Guilloteau, J., Mathieu, M., Giglione, C., Blanc, V., Dupuy, A., Chevrier, M., Gil, P., Famechon, A., Meinnel, T., and Miko, V., The Crystal Structures of Four Peptide Deformylases Bound to the Antibiotic Actinonin Reveal Two Distinct Types: A Platform for the Structure-based Design of Antibacterial Agents. J. Mol. Biol., 320, 951–962 (2002).
Ho, C. Y., Strobel, E., Ralbovsky, J., and Galemmo. R. A., Improved solution- and solid-phase preparation of hydroxamic acids from esters. J. Org. Chem., 70, 4873–4875 (2005).
Jain, R., Chen, D., White, R. J., Patel, D. V., and Yuan, Z., Bacterial peptide deformylase inhibitors: A new class of antibacterial agents. Curr. Med. Chem., 12, 1607–1621 (2005).
Kamiski, Z. J., 2-Chloro-4,6-dimethoxy-1,3,5-triazine. A new coupling reagent for peptide synthesis. Synthesis, 1987, 917–920 (1987).
Koneman, E. W., Allen, S. D., and Winn, W. C., Color atlas and textbook of diagnostic microbiology. Lippincott Raven Pub, Philadelphia, pp. 86–856, (1997).
Lee, M. D., She, Y., Soskis, M. J., Borella, C. P., Gardner, J. R., Hayes, P.A., Dy, B. M., Heaney, M. L., Philips, M. R., Bornmann, W. G., Sirotnak, F. M., and Scheinberg, D. A., Human mitochondrial peptide deformylase, a new anticancer target of actinonin-based antibiotics. J. Clin. Invest., 114, 1107–1116 (2004).
Levy, D. E., Lapierre, F., Liang, W., Ye, W., Lange, C. W., Li, X., Grobelny, D., Terrell, M., Holme, K., Nadzan, A., and Galardy, R. E., Matrix Metalloproteinase Inhibitors: A StructureActivity Study. J. Med. Chem., 41, 199–223 (1998).
Lofland, D., Difuntorum, S., Waller, A., Clements, J. M., Weaver, M. K., Karlowsky, J. A., and Johnson, K., In vitro antibacterial activity of the peptide deformylase inhibitor BB-83698. J. Antimicrob. Chemother., 53, 664–668 (2004).
Madison, V., Duca, J., Bennett, F., Bohanon, S., Cooper, A., Chu, M., Desai, J., Girijavallabhan, V., Hare, R., Hruza, A., Hendrata, S., Huang, Y., Kravec, C., Malcolm, B., McCormick, J., Miesel, L., Ramanathan, L., Reichert, P., Saksena, A., Wang, J., Weber, P. C., Zhu, H., and Fischmann, T., Binding affinities and geometries of various metal ligands in peptide deformylase inhibitors. Biophys. Chem., 101–102, 239–247 (2002).
National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically. Approved Standard, Sixth Edition; NCCLS documents M7-A6. National Committee for Clinical Laboratory Standards, Wayne, Pa, (2003).
Penning, T. D., Khilevich, A., Chen, B. B., Russell, M. A., Boys, M. L., Wang, Y., Duffin, T., Engleman, V. W., Finn, M. B., Freeman, S. K., Hanneke, M. L., Keene, J. L., Klover, J. A., Nickols, G. A., Nickols, M.A., Rader, R. K., Settle, S. L., Shannon, K. E., Steininger, C. N., Westlinc, M. M., and Westlin, W. F., Synthesis of pyrazoles and isoxazoles as potent αvβ3 receptor antagonists. Bioorg. Med. Chem. Lett., 16, 3156–3161 (2006).
Reddy, A. S., Kumar, M. S., and Reddy, G. R., A convenient method for the preparation of hydroxamic acids. Tetrahedron Lett., 41, 6285–6288 (2000).
Shen, G., Zhu, J., Simpson, A. M., and Pei, D., Design and synthesis of macrocyclic peptidyl hydroxamates as peptide deformylase inhibitors. Bioorg. Med. Chem. Lett., 18, 3060–3063 (2008).
Smith, H. K., Beckett, R. P., Clements, J. M., Doel, S., East, S. P., Launchbury, S. B., Pratt, L. M., Spavold, Z. M., Thomas, W., Todd, R. S., and Whittaker, M., Structureactivity relationships of the peptide deformylase inhibitor BB-3497: modification of the metal binding group. Bioorg. Med. Chem. Lett., 12, 3595–3599 (2002).
Spratt, B. G., Resistance to antibiotics mediated by target alterations BG Spratt. Science, 264, 388–393 (1994).
Yuan, Z., Trias, J., and White, R. J., Deformylase as a novel antibacterial target. Drug Discov. Today, 6, 954–961 (2001).
Zhang, D. T., Tang, L. D., Duan, G. Y., Zhao, G. L., Xu, W. R., Meng, L. J., and Wang. J. W., Synthesis, resolution, and enantiomeric purity assay of 2-n-butylbutanedioic acid 4-t-butyl esters. Chem. Res. Chin. Univ., 22, 584–588 (2006).
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Zhang, D., Jia, J., Meng, L. et al. Synthesis and preliminary antibacterial evaluation of 2-butyl succinate-based hydroxamate derivatives containing isoxazole rings. Arch. Pharm. Res. 33, 831–842 (2010). https://doi.org/10.1007/s12272-010-0605-7
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DOI: https://doi.org/10.1007/s12272-010-0605-7