Compounds which interfere with microbial quorum sensing mechanism for use as anti-infective and immunomodulatory agents.

The General Hospital Corporation & INRS Institut Armand Frappier (2006). Compounds which interfere with microbial quorum sensing mechanism for use as anti-infective and immunomodulatory agents. WO 2006/130832 A2.

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Résumé

The present invention provides compds. I (R1 = (substituted)C1-12-alkyl, C1-4-alkaryl, etc. ; R2,R3 = H, (substituted))C1-6-alkyl, C1-4-alkaryl, etc., or R2, R3 and the N to which they are bound form NO2; R4 = H, halo, OH, C1-6-alkoxy; R5-7 = R4, C1-6-alkyl; X = R4, NR2R3; Y = R4, R5, NR2R3; Z = R5, NR2R3) and II (R1,R4-6 same as in I; R8 = R1; R9 = H, OH, (substituted)C1-6-alkoxy, etc.), pharmaceutical compns. contg. I and II, and methods that include the use of I and II as anti-infective compds. that potentiate the host immune response or limit or prevent the expression or activity of individual virulence factors. In addn., the compns. have immunomodulatory activity, and therefore can be used to prime host defenses to prevent or limit bacterial, fungal, and viral viability. In the compns. and methods of the inventions, the quorum sensing mechanism is targeted to prevent pathogenesis (e.g., infection). Such an approach should prevent pathogenic organisms from acquiring resistance to the protective anti-infective compds. Thus, compds. such as 6-fluoro-2-aminobenzoic acid and 4-chloro-2-aminobenzoic acid were potent inhibitors of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinoline prodn. The compd. 2-aminoacetophenone (2AA), when injected into the burn eschar of burned and P. aeruginosa-infected mice, reduced mortality. 2AA inhibited expression of the pqs operon by competing with transcription factor MvfR activators 4-hydroxy-2-heptylquinoline and 3,4-dihydroxy-2-heptylquinoline. P. aeruginosa genes downregulated by 2AA and mouse genes induced by 2AA were identified

Type de document:	Brevet
Mots-clés libres:	Allergy inhibitors;, Anti-infective agents; Antitumor agents; Autoimmune disease; Bacterial infection; Immunostimulants; Mycosis; Neoplasm; Quorum sensing
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	01 mai 2014 20:42
Dernière modification:	12 févr. 2015 20:42
URI:	https://espace.inrs.ca/id/eprint/2235

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