Senior Suzanne J, Illarionov Petr A, Gurcha Sudagar S, Campbell Ian B, Schaeffer Merrill L, Minnikin David E, Besra Gurdyal S
School of Biosciences, The University of Birmingham, B15 2TT, Edgbaston, Birmingham, UK
Bioorg Med Chem Lett. 2004 Jan 19;14(2):373-6. doi: 10.1016/j.bmcl.2003.10.061.
Analogues of the natural antibiotic thiolactomycin, with acetylene-based side chains, have the highest recorded in vitro inhibitory activity against the recombinant Mycobacterium tuberculosis beta-ketoacyl-ACP synthase mtFabH condensing enzyme. In particular, 5-[3-(4-acetyl-phenyl)-prop-2-ynyl]-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one exhibited more than an 18-fold increased potency, compared to thiolactomycin, against this key condensing enzyme, involved in M. tuberculosis mycolic acid biosynthesis. Analogues of the antibiotic thiolactomycin, with acetylene-based side chains, have the highest recorded activity against cloned mtFabH condensing enzyme.
具有乙炔基侧链的天然抗生素硫代乳霉素类似物，对重组结核分枝杆菌β-酮酰基-ACP合酶mtFabH缩合酶具有有记录以来最高的体外抑制活性。特别是，5-[3-(4-乙酰基苯基)-丙-2-炔基]-4-羟基-3,5-二甲基-5H-噻吩-2-酮与硫代乳霉素相比，对参与结核分枝杆菌分枝菌酸生物合成的这种关键缩合酶的效力提高了18倍以上。具有乙炔基侧链的抗生素硫代乳霉素类似物，对克隆的mtFabH缩合酶具有有记录以来最高的活性。
