Design, synthesis and structure-activity relationship of novel Relacin analogs as inhibitors of Rel proteins

European Journal of Medicinal Chemistry

Volumn 70, Issue , 2013, Pages 497-504

  Wexselblatt, Ezequiel ^a   Kaspy, Ilana ^a   Glaser, Gad ^a   Katzhendler, Joshua ^a   Yavin, Eylon ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

(p)ppGpp; Antibacterial; Purine; RelA; Stringent Response

Indexed keywords

2 [[[[2 (DIMETHYLAMINO)ETHYL]CARBAMOYL]OXY]METHYL] 5 (2 ISOBUTYRAMIDO 6 OXO 1,6 DIHYDRO 9H PURIN 9 YL)TETRAHYDORURAN 3 YL[2 (DIMETHYLAMINO)EHTYL]CARBAMATE; 6 [[[[3 [[(5 CARBOXYPENTYL)CARBAMOYL]OXY] 5 (2 ISOBUTYRAMIDO 6 OXO 1,6 DIHYDRO 9H PURIN 9 YL)TETRAHYDROFURAN 2 YL]METHOXY]CARBONYL]AMINO HEAXANOIC ACID; BENZYL 6 [[[[3 [[[6 (BENZYLOXY) 6 OXOHEXYL]CARBAMOYL]OXY] 5 (2 ISOBUTYRAMIDO 6 OXO 1,6 DIHYDRO 9H PURIN 9 YL) TETRAHYDROFURAN 2 YL]METHOXY]CARBONYL]AMINO]HEXONOATE; BENZYL[[[3 [[[2 (BENZYLOXY) 2 OXOETHYL]CARBAMOYL] OXY] 5 (2 ISOBUTYRAMIDO 6 OXO 1,6 DIHYDRO 9H PURIN 9 YL)TETRAHYDROFURAN 2 YL]METHOXY]GLYCINATE; DIBENZYL[[[3 [[[1,5 BIS(BENZYLOXY) 1,5 BIS(BENZYLOXY) 1,5 DIOXOPENTAN 2 YL]CARBAMOYL]OXY] 5 (2 ISOBUTYRAMIDO 6 OXO 1,6 DIHYDRO 9H PURIN 9 YL)TETRAHYDROFURAN 2 YL]METHOXY]CARBONYL]GLUTAMATE; PROTEIN INHIBITOR; RELACIN DERIVATIVE; TRANSCRIPTION FACTOR REL; TRIBENZYL[[[3 [[(GLUTAMYLGLUTAMATE)CARBAMOYL]OXY] 5 (2 ISOBUTYRAMIDO 6 OXO 1,6 DIHYDRO 9H PURIN 9 YL) TETRAHYDROFURAN 2 YL]METHOXY]CARBONYL]GLUTAMYLGLUTAMATE; UNCLASSIFIED DRUG; [[[3 [[(1,3 DICARBOXYPROPYL)CARBAMOYL]OXY] 5 (2 ISOBUTYRAMIDO 6 OXO 1,6 DIHYDRO 9H PURIN 9 YL)TETRAHYDROFURAN 2 YL]METHOXY]CARBONYL]GLUTAMIC ACID; [[[3 [[(CARBOXYMETHYL)CARBAMOYL]OXY] 5 (2 ISOBUTYRAMIDO 6 OXO 1,6 DIHYDRO 9H PURIN 9 YL)TETRAHYDROFURAN 2 YL]METHOXY]CARBONYL]GLYCINE;

ARTICLE; BACILLUS SUBTILIS; BACTERIAL SURVIVAL; COLUMN CHROMATOGRAPHY; COMPARATIVE STUDY; DRUG DESIGN; DRUG SYNTHESIS; GRAM NEGATIVE BACTERIUM; HYDROGEN BOND; HYDROGENOLYSIS; STRUCTURE ACTIVITY RELATION;

(P)PPGPP; ANTIBACTERIAL; PURINE; RELA; STRINGENT RESPONSE;

DEINOCOCCUS; DEOXYGUANOSINE; DIPEPTIDES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; ESCHERICHIA COLI; MOLECULAR STRUCTURE; PROTO-ONCOGENE PROTEINS C-REL; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84886738771     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2013.10.036     Document Type: Article

References (20)

1. V. Jain, M. Kumar, and D. Chatterji ppGpp: stringent response and survival J. Microbiol. 44 2006 1 10 (Pubitemid 44891239)
2. J.A.C. Lemos, T.A. Brown, and R.A. Burne Effects of RelA on key virulence properties of planktonic and biofilm populations of Streptococcus mutans Infect. Immun. 72 2004 1431 1440 (Pubitemid 38263765)
3. K. Ochi, J.C. Kandala, and E. Freese Initiation of Bacillus subtilis sporulation by the stringent response to partial amino-acid deprivation J. Biol. Chem. 256 1981 6866 6875 (Pubitemid 11010849)
4. K. Potrykus, and M. Cashel ppGpp: still magical? Annual Review of Microbiology 2008 35 51
5. M. Cashel, and J. Gallant Two compounds implicated in the function of the RC gene of Escherichia coli Nature 221 1969 838 841
6. S. Metzger, E. Sarubbi, G. Glaser, and M. Cashel Protein sequences encoded by the relA and the spoT genes of Escherichia coli are interrelated J. Biol. Chem. 264 1989 9122 9125 (Pubitemid 19157539)
7. T.M. Wendrich, and M.A. Marahiel Cloning and characterization of a relA/spoT homologue from Bacillus subtilis Mol. Microbiol. 26 1997 65 79 (Pubitemid 27438238)
8. M. Cashel, D.M. Gentry, V.J. Hernandez, and D. Vinella The stringent response F.C. Neidhardt, Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology second ed. 1996 ASM Press 1458 1496
9. T.M. Wendrich, G. Blaha, D.N. Wilson, M.A. Marahiel, and K.H. Nierhaus Dissection of the mechanism for the stringent factor RelA Mol. Cell 10 2002 779 788 (Pubitemid 35335633)
10. T. Hogg, U. Mechold, H. Malke, M. Cashel, and R. Hilgenfeld Conformational antagonism between opposing active sites in a bifunctional RelA/SpoT homolog modulates (p)ppGpp metabolism during the stringent response Cell 117 2004 57 68 (Pubitemid 38469898)
11. T.D. Bugg, A.J. Lloyd, and D.I. Roper Phospho-MurNAc-pentapeptide translocase (MraY) as a target for antibacterial agents and antibacterial proteins Infect. Disord. Drug Targets 6 2006 85 106 (Pubitemid 43881018)
12. +-dependent DNA ligase inhibitors with broad-spectrum activity and antibacterial efficacy in vivo Antimicrob. Agents Chemother. 55 2011 1088 1096
13. A. Talukdar, Y. Zhao, W. Lv, A. Bacher, B. Illarionov, M. Fischer, and M. Cushman O-Nucleoside, S-nucleoside, and N-nucleoside probes of lumazine synthase and riboflavin synthase J. Org. Chem. 77 2012 6239 6261
14. K. Clinch, G.B. Evans, R.F. Frohlich, S.A. Gulab, J.A. Gutierrez, J.M. Mason, V.L. Schramm, P.C. Tyler, and A.D. Woolhouse Transition state analogue inhibitors of human methylthioadenosine phosphorylase and bacterial methylthioadenosine/S-adenosylhomocysteine nucleosidase incorporating acyclic ribooxacarbenium ion mimics Bioorg. Med. Chem. 20 2012 5181 5187
15. A. Bzowska, E. Kulikowska, and D. Shugar Purine nucleoside phosphorylases: properties, functions, and clinical aspects Pharmacol. Ther. 88 2000 349 425 (Pubitemid 32406058)
16. A. Gupte, H.I. Boshoff, D.J. Wilson, J. Neres, N.P. Labello, R.V. Somu, C. Xing, C.E. Barry, and C.C. Aldrich Inhibition of siderophore biosynthesis by 2-triazole substituted analogues of 5′-O-[N-(salicyl)sulfamoyl]adenosine: antibacterial nucleosides effective against Mycobacterium tuberculosis J. Med. Chem. 51 2008 7495 7507
17. E. Wexselblatt, J. Katzhendler, R. Saleem-Batcha, G. Hansen, R. Hilgenfeld, G. Glaser, and R.R. Vidavski ppGpp analogues inhibit synthetase activity of Rel proteins from Gram-negative and Gram-positive bacteria Bioorg. Med. Chem. 18 2010 4485 4497
18. E. Wexselblatt, Y. Oppenheimer-Shaanan, I. Kaspy, N. London, O. Schueler-Furman, E. Yavin, G. Glaser, J. Katzhendler, and S. Ben-Yehuda Relacin, a novel antibacterial agent targeting the Stringent Response PLoS Pathog. 8 2012 e1002925
19. V.A. Korshun, D.A. Stetsenko, and M.J. Gait Novel uridin-2[prime or minute]-yl carbamates: synthesis, incorporation into oligodeoxyribonucleotides, and remarkable fluorescence properties of 2[prime or minute]-pyren-1- ylmethylcarbamate J. Chem. Soc. Perkin Trans. 1 2002 1092 1104
20. T. Nakata, M. Takahashi, M. Nakatani, R. Kuramitsu, M. Tamura, and H. Okai Role of basic and acidic fragments in delicious peptides (Lys-Gly-Asp-Glu-Glu-Ser-Leu-Ala) and the taste behavior of sodium and potassium salts in acidic oligopeptides Biosci. Biotechnol. Biochem. 59 1995 689 693