Title of article :
Synthesis and biological evaluation of a C5-biphenyl thiolactomycin library
Author/Authors :
Veemal Bhowruth، نويسنده , , Alistair K. Brown، نويسنده , , Suzanne J. Senior، نويسنده , , John S. Snaith، نويسنده , , Gurdyal S. Besra، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2007
Abstract :
Fifteen novel C5 analogues of thiolactomycin (13 biphenyl analogues and two biphenyl mimics) have been synthesised and assessed for their in vitro mtFabH and whole cell Mycobacterium bovis BCG activity, respectively. Analysis of the 15 compounds revealed that six possessed enhanced in vitro activity in a direct mtFabH assay. Encouragingly analogues 11, 12 and 13 gave a significant enhancement in in vitro activity against mtFabH. Analogue 13 (5-(4-methoxycarbonyl-biphenyl-4-ylmethyl)-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one) gave an IC50 value of 3 μM compared to the parent drug thiolactomycin (75 μM) against mtFabH. The biological analysis of this library reaffirms the requirement for a linear π-rich system containing hydrogen bond accepting substituents attached to the para-position of the C5 biphenyl analogue to generate compounds with enhanced activity.
Keywords :
Mycobacterium bovis BCG , Mycobacterium tuberculosis , mycolic acids , inhibitors , Thiolactomycin
Journal title :
Bioorganic & Medicinal Chemistry Letters
Journal title :
Bioorganic & Medicinal Chemistry Letters