Synthesis and biological evaluation of a C5-biphenyl thiolactomycin library |
| |
Authors: | Bhowruth Veemal Brown Alistair K Senior Suzanne J Snaith John S Besra Gurdyal S |
| |
Affiliation: | School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. |
| |
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 IC(50) value of 3 microM compared to the parent drug thiolactomycin (75 microM) against mtFabH. The biological analysis of this library reaffirms the requirement for a linear pi-rich system containing hydrogen bond accepting substituents attached to the para-position of the C5 biphenyl analogue to generate compounds with enhanced activity. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|