Discovery of novel antibacterial agents active against methicillin-resistant Staphylococcus aureus from combinatorial benzopyran libraries

ChemBioChem

Volumn 2, Issue 6, 2001, Pages 460-465

  Nicolaou, K C ^a,b   Roecker, A J ^a,b   Barluenga, Sofia ^a,b   Pfefferkorn, Jeffrey A ^a,b   Cao, Guo Qiang ^a,b  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Antibiotics; Benzopyrans; Combinatorial chemistry; Stilbenes; Structure activity relationships

Indexed keywords

ANTIINFECTIVE AGENT; BENZOPYRAN DERIVATIVE;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; COMBINATORIAL CHEMISTRY; DRUG EFFECT; PENICILLIN RESISTANCE; PHYSIOLOGY; STAPHYLOCOCCUS AUREUS; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ANTI-BACTERIAL AGENTS; BENZOPYRANS; COMBINATORIAL CHEMISTRY TECHNIQUES; METHICILLIN RESISTANCE; MOLECULAR STRUCTURE; STAPHYLOCOCCUS AUREUS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0035382954     PISSN: 14394227     EISSN: None     Source Type: Journal    
DOI: 10.1002/1439-7633(20010601)2:6<460::AID-CBIC460>3.0.CO;2-2     Document Type: Article

References (20)

1. For a review, see C. Walsh, Nature 2000, 406, 775-781.
2. For reviews, see a) D. H. Williams, B. Bardsley, Angew. Chem. 1999, 111, 1264-1286;
3. Angew. Chem. Int. Ed. 1999, 38, 1172-1193;
4. b) K. C. Nicolaou, C. N. C. Boddy, S. Bräse, N. Winssinger, Angew. Chem. 1999, 111, 2230-2287;
5. Angew. Chem. Int. Ed. 1999, 38, 2097-2152.
6. For a review, see D. T. W. Chu, J. J. Plattner, L. Katz, J. Med. Chem. 1996, 39, 3853-3874.
7. K. C. Nicolaou, J. A. Pfefferkorn, A. J. Roecker, G.-Q. Cao, S. Barluenga, H. J. Mitchell, J. Am. Chem. Soc. 2000, 122, 9939-9953.
8. K. C. Nicolaou, J. A. Pfefferkorn, H. J. Mitchell, A. J. Roecker, S. Barluenga, G.-Q. Cao, R. L. Affleck, J. E. Lillig, J. Am. Chem. Soc. 2000, 122, 9954-9967.
9. K. C. Nicolaou, J. A. Pfefferkorn, S. Barluenga, H. J. Mitchell, A. J. Roecker, G.-Q. Cao, J. Am. Chem. Soc. 2000, 122, 9968-9976.
10. Compounds of this general structure have been previously reported as phosphodiesterase IV inhibitors, see: B. Gutterer, D. Flockerzi, H. Amschler, W.-R. Ulrich, T. Bar, T. Martin, A. Hatzelmann, H. Boss, R. Beume, D. Hafner, H.-P. Kley (Byk Gulden Lomberg Chemische Fabrik GmbH, Germany), EP 96-111557 19960718; [Chem. Abstr. 1998, 128, 140610].
11. Several other types of stilbenes have been reported to exhibit antimicrobial properties. For leading references, see: a) E. Wyrzykiewicz, A. Blaszczyk, B. Kedzia. Farmaco 2000, 55, 151-157;
12. b) E. Wyrzykiewicz, W. Prukala, B. Kedzia, Farmaco 1994, 49, 127-131.
13. -1 and all experiments were conducted in triplicate. The MIC value was taken to be the lowest concentration that inhibited visible growth of the microorganism after 24 h at 37 °C. SA 6538, SA 13709, MRSA 33591, and MRSA 43300 were grown in Trypticase Soy Broth (BBL 11043). SA 29213, MRSA 700787, MRSA 700788, and MRSA 700778 were grown in Mueller-Hinton broth (Difco 0757). MRSA 700698 and EF 6057 were grown in Brain Heart Infusion broth (Difco 237400). For representative testing procedure, see: A. M. Clark, F. S. El Feraley, W. S. Li, J. Pharm. Sci. 1981, 70, 951-952.
14. C. Z. Ding, Syn. Commun. 1996, 26, 4267-4273.
15. F. Ladhar, R. El Gharbi, Syn. Commun. 1991, 21, 413-417.
16. J. A. Wytko, J. Weiss, J. Org. Chem. 1990, 55, 5200-5202.
17. For the synthesis of trichloroacetimidates see ref. [4].
18. C. D. Gabbutt, J. D. Hepworth, B. M. Heron, M. M. Rahman, J. Chem. Soc. Perkin Trans. 1 1994, 1733-1737.
19. R. Camps, J. Coll, A. Messeguar, M. A. Pericas, Tetrahedron Lett. 1980, 21, 2361-2364.
20. Interest in glycosidated analogues was a result of the sporadic activity of compounds of this type in the original screening library.