Antimicrobial Lexitropsins
Journal of Medicinal Chemistry, 2007, Vol. 50, No. 24 6125
(6) Anthony, N. G.; Fox, K. R.; Johnston, B. F.; Khalaf, A. I.; Mackay,
S. P.; McGroarty, I. S.; Parkinson, J. A.; Skellern, G. G.; Suckling,
C. J.; Waigh, R. D. DNA binding of a short lexitropsin. Bioorg. Med.
Chem. Lett. 2004, 14, 1353-1356.
(7) Haq, I.; Ledbury, J. E.; Chowdrhy, B. Z.; Jenkins, T. C.; Chaires, J.
B. Specific binding of Hoechst 33258 to the (CGCAAATTTGCG)2
duplex: calorimetric and spectroscopic studies. J. Mol. Biol. 1997,
271, 244-257.
(8) Kirschner, D. Timebomb: the global epidemic of multi-drug resistant
tuberculosis. Nat. Med. 2001, 7, 1173.
(26) (a) Turin, L. M.; Pitt, A. R.; Suckling, C. J.; Waigh, R. W. Covalently
linked dimeric DNA binding molecules. Genelabs Tech., Inc.
WO0119792, 2001. (b) Zhang, W.; Liehr, S. J. R.; Velligan, M. D.;
Dyatkina, N. B.; Botyanszki, J.; Shi, D.-F.; Roberts, C. D.; Khorlin,
A.; Nelson, P. H.; Muchowski, J. M. Genelabs Tech., Inc. WO0200650,
2002.
(27) Khalaf, A. I.; Waigh, R. D.; Drummond, A. J.; Pringle, B.;
McGroarty, I.; Skellern, G. G.; Suckling, C. J. Distamycin analogues
with enhanced lipophilicity. J. Med. Chem. 2004, 47, 2133-2156.
(28) Fedier, A.; Fowst, C.; Tursi, J.; Geroni, C.; Haller, U.; Marchini, S.;
Fink, D. Brostacillin (PNU-166196)sa new DNA minor groove
binder retains sensitivity in DNA mismatch repair-deficient tumour
cells. Br. J. Cancer 2003, 89, 1559-1565.
(29) ten Tije, A. J.; Verweij, J.; Sparreboom, A.; van der Gaast, A.; Fowst,
C.; Fiorentini, F.; Tursi, J.; Antonellini, A.; Mantel, M.; Hartman,
C. M.; Stoter, G.; Planting, A. S. T.; De Jonge, M. J. A. Phase I and
pharmacokinetic study of brostacillin (PNU-166196), a new DNA
minor groove binder, administered intravenously every 3 weeks to
adult patients with metastatic cancer. Clin. Cancer Res. 2003, 9,
2957-2964.
(30) Lansiaux, A.; Tanious, F.; Mishal, Z.; Dassonneville, L.; Kumar, A.;
Stephens, C. E.; Hu, Q.; Wilson, W. D.; Boykin, D. W.; Bailly, C.
Distribution of furamidine analogues in tumor cells: targeting of the
nucleus or mitochondria depending on the amidine substitution.
Cancer Res. 2002, 62, 7219-7229.
(31) Taylor, A.; Webster, K. A.; Gustafson, T. A.; Kedes, L. The anti-
cancer agent distamycin A displaces essential transcription factors
and selectively inhibits myogenic differentiation distamycin. Mol.
Cell Biochem. 1997, 169, 61-72.
(32) Ellis, E.; Ford, G.; Hunter, I. S. Unpublished results.
(33) Gemmell, C. G.; Goutcher, S. C.; Reid, R.; Sturrock, R. D. Role of
certain virulence factors in a murine model of Staphylococcus aureus
arthritis. J. Med. Microbiol. 1997, 46, 208-213.
(34) Drummond, A. J.; Waigh, R. D. The development of microbiological
methods for phytochemical screening. Recent Res. DeVel. Phytochem.
2000, 4, 143-152.
(35) Khalaf, A. I.; Pitt, A. R.; Scobie, M.; Suckling, C. J.; Urwin, J.;
Waigh, R. D.; Young, S. C.; Fishleigh, R. V.; Wylie, W. A. The
synthesis of some head to head linked minor groove binders.
Tetrahedron 2000, 56, 5225-5239.
(9) Applebaum, P. C. MRSAsthe tip of the iceberg Clin. Microbiol.
Infect. 2006, 12, 3-10, Suppl. 2.
(10) Suckling, C. J. Minor groove binders 1998-2004: a review of the
patent literature. Expert Opin. Ther. Pat. 2004, 14, 1693-1724.
(11) Kaizerman, J. A.; Gross, M. I.; Ge, Y.; White, S.; Hu, W.; Duan,
J.-X.; Baird, E. E.; Johnson, K. W.; Tanaka, R. D.; Moser, H. E.;
Bu¨rli, R. W. DNA binding ligands targeting drug-resistant bacteria:
structure, activity, and pharmacology. J. Med. Chem. 2003, 46, 3914-
3929.
(12) Bu¨rli, W.; R.; Ge, Y.; White, S.; Touami, S. M.; Taylor, M.;
Kaizerman, J. A.; Moser, H. E. DNA binding ligands with excellent
antibiotic potency against drug-resistant Gram-positive bacteria.
Bioorg. Med. Chem. Lett. 2002, 12, 2591-2594.
(13) Bu¨rli, R. W.; Mcminn, D.; Kaizerman, J. A.; Hu, W.; Ge, Y.; Pack,
Q.; Jiang, V.; Gross, M.; Garcia, M.; Tanaka, R.; Moser, H. E. DNA
binding ligands targeting drug-resistant Gram-positive bacteria. Part
1: Internal benzimidazole derivatives. Bioorg. Med. Chem. Lett. 2004,
14, 1253-1257.
(14) Bu¨rli, R. W.; Jones, P.; Mcminn, D.; Le, Q.; Duan. J.-X.; Kaizerman,
J. A.; Difuntorum, S.; Moser, H. E. DNA binding ligands targeting
drug resistant Gram-positive bacteria. Part 2: C-terminal benzimi-
dazoles and derivatives. Bioorg. Med. Chem. Lett. 2004, 14, 1259-
1263.
(15) Bu¨rli, R. W.; Kaizerman, J. A; Duan, J.-X.; Jones, P.; Johnson, K.
W.; Iwamoto, M.; Truong, K.; Hu, W.; Stanton, T.; Chen, A.; Touami,
S.; Gross, M.; Jiang, V.; Ge, Y.; Moser, H. E. DNA binding ligands
with in vivo efficacy in murine models of bacterial infection:
optimization of internal aromatic amino acids. Bioorg. Med. Chem.
Lett. 2004, 14, 2067-2072.
(16) Dyatkina, N. B.; Roberts, C. D.; Keicher, J. D.; Dai, Y.; Nadherny,
J. P.; Zhang, W.; Schmitz, U.; Kongpachith, A.; Fung, K.; Novikov,
A. A.; Lou, L.; Velligan, M.; Khorlin, A. A.; Chen, M. S. Minor
groove binders as antibacterial agents. 1. Pyrrole tetraamides are
potent antibacterial agents against vancomycin resistant Enterococci
and methicillin resistant Staphylococcus aureus. J. Med. Chem. 2002,
45, 805-817.
(17) (a) Khalaf, A. I.; Pitt, A. R.; Scobie, M.; Suckling, C. J.; Urwin, J.;
Waigh, R. D.; Young, S. C.; Fishleigh, R. V.; Fox, K. R. Design
and synthesis of extended lexitropsins with good solubility and
potentially improved tissue penetration characteristics. J. Med. Chem.
2000, 43, 3257-3266. (b) Khalaf, A. I.; Suckling, C. J.; Waigh, R.
D. Novel hydrophobic minor groove agents. U.K. Pat. Appl.
0619325.4, 2006.
(18) Anthony, N. G.; Johnston, B. F.; Khalaf, A. I.; Mackay, S. P.;
Parkinson, J. A.; Suckling, C. J.; Waigh, R. D. A short lexitropsin
that recognizes the DNA minor groove at 5-ACTAGT-3: Under-
standing the role of isopropyl-thiazole. J. Am. Chem. Soc. 2004, 126,
11338-11349.
(19) Yamamoto, Y.; Kimachi, T.; Kanaoka, Y.; Kato, S.; Bessho, K.
Synthesis and DNA binding properties of amide bond-modified
analogues related to distamycin. Tetrahedron Lett. 1996, 37, 7801-
7804.
(36) Gupton, J. T.; Krolikowski, D. A.; Yu, R. H.; Riesinger, S. W.;
Sikorski, J. A. Application of 2-substituted vinamidinium salts to
the synthesis of 2,4-disubstituted pyrroles J. Org. Chem. 1990, 55,
4735-4740.
(37) Grehn, L. Preparative aspects of the nitration of 1-methylpyrrole
derivativessC-13 NMR of some nitropyrroles. Chemica Scripta,
1979, 13, 67-77.
(38) Inami, K.; Shiba, T. Total synthesis of antibiotic Althiomycin. Bull.
Chem. Soc. Jpn. 1985, 58, 352.
(39) Li, W-D. Z.; Wei, K. Intramolecular alkylative arylation of oxabicylic
alkene: a potential diene approach for the synthesis of estrone and
analogous steroid structures. Org. Lett. 2004, 6, 1333-1335.
(40) Cluzan, R.; Katz, L. Esters of substituted nicotinic acids. The Boots
Company Ltd. U.S. 4,009,174, 1977.
(41) Nielsen, C. B.; Johnsen, M.: Arnbierg, J.; Pittelkow, M.; McIlroy,
S. P.; Ogilby, P. R.; Jorgensen, M. Synthesis and characterisation of
water-soluble pH enylene-vinylene-based singlet oxygen sensitizers
for two photon excitation. J. Org. Chem. 2005, 70, 7065-7079.
(42) Uno, H.; Kurokawa, M.; Masuda, Y. Syntheses of 2-sulfamoyl-
methylbenzoxazole derivatives and determination of their anticon-
vulsant activity. Chem. Pharm. Bull. 1981, 29, 2359-2361.
(43) Kosaka, T.; Wakabayashi, T. Synthesis of 2-(4-aryl-1E,3E-butadi-
enyl)benzoxazoles by the Horner-Wadsworth-Emmons reaction.
Heterocycles 1995, 41, 477-486.
(44) Ramana, D. V.; Krishna, N. V. S. R. Ortho interactions and
intramolecular aromatic substitutions in 2-(styryl)benzazoles under
electron-impact. Indian J. Chem., Sect. B 1990, 21, 247-252.
(45) Rao, K. E.; Bathini, Y.; Lown, J. W. Synthesis of novel thiazole-
containing DNA minor groove binding oligopeptides related to the
antibiotic distamycin. J. Org. Chem. 1990, 55, 728-737.
(46) Grammaticakis, P. Medium ultraviolet and visible absorbsion of
N-aroylarylamines. Bull. Soc. Chim. France 1964, 924-935.
(47) Drefahl, G.; Gerlach, E. γ-Stilbazole-4′-aldehyde and γ-stilbazole-
4′-carboxylic acid. J. Prakt. Chem. 1958, 6, 72-79.
(20) Nuhn, P.; Buege, A.; Harenberg, P.; Lettau, H.; Moschner, K.;
Bauchmaul, M.; Schneider, R. Synthesis of lipoxygenase inhibitors.
1. Synthesis of open amidrazones Pharmazie 1993, 48, 340-342.
(21) Walczynski, K.; Timmerman, H.; Zuiderveld, O. P.; Zhang, M. Q.;
Glinka, R. Histamine H-1 receptor ligands Part I. Novel thiazol-4-
ylethanamine derivatives: synthesis and in vitro pharmacology.
Farmaco 1999, 54, 533-541.
(22) Reynaud, P.; Moreau, R. C.; Thu, N. H. A property of primary
thioamides. C. R. Sci. 1961, 253, 1968-1970.
(23) Freydank, A. C.; Humphrey, M. G.; Friedrich, R. W.; Luther-Davies,
B. Synthesis and optical characterization of unsymmetrical oligophe-
nylenevinylenes. Tetrahedron 2002, 58, 1425-1432.
(24) Lehrfeld, J.; Burkman, A. M.; Gearien, J. E. Synthesis of 6-substituted
nicotinic acid derivatives as analogues of ergot alkaloids. J. Med.
Chem. 1964, 7, 150-154.
(25) Khalaf, A. I.; Ebrahimabadi, A. H.; Drummond, A. J.; Anthony, N.
G.; Mackay, S. P.; Suckling, C. J.; Waigh, R. D. Synthesis and
antimicrobial activity of some netropsin analogues Org. Biomol.
Chem. 2004, 2, 3119-3127.
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