Please use this identifier to cite or link to this item: http://hdl.handle.net/10216/97586
Author(s): Stanislav Gobec
Ivan Plantan
Janez Mravljak
Urban Svajger
Rosalind A Wilson
Gurdyal S Besra
Sousana L Soares
Rui Appelberg
Danijel Kikelj
Title: Design, synthesis, biochemical evaluation and antimycobacterial action of phosphonate inhibitors of antigen 85C, a crucial enzyme involved in biosynthesis of the mycobacterial cell wall
Issue Date: 2007
Abstract: Phosphonate inhibitors of antigen 85C were prepared. The inhibitors, comprising a phosphonate moiety, mycolic acid mimetic and a trehalose surrogate, contain substituted benzyl alcohols, N-(omega-hydroxyalky)phthalimide, 2-phenylethanol or 4-(phthalimido)butanol as trehalose mimetics, and an alkyl chain of different lengths mimicking the mycolic acid side chain. The best compounds inhibited the mycolyltransferase activity of antigen 85C With IC50 in the low micromolar range and inhibited the growth of Mycobacterium avium in culture. The best compounds in the 3-phenoxybenzyl- and omega-(phthalimido)alkoxy series, ethyl 3-phenoxybenzyl butylphosphonate (4a) and (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) methyl ethyl heptylphosphonate (5c) displayed IC50 values of 2.0 and 1.3 mu M, respectively, in a mycolyltransferase inhibition assay. In a M. avium growth inhibition assay MIC of 4a and (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl ethyl nonylphosphonate (5d) were 248.8 and 84.5 mu g/mL, respectively.
Subject: Ciências da Saúde, Medicina básica
Health sciences, Basic medicine
Call Number: 88560
URI: http://hdl.handle.net/10216/97586
Document Type: Artigo em Revista Científica Internacional
Rights: restrictedAccess
Appears in Collections:ICBAS - Artigo em Revista Científica Internacional

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