Institute of Life Sciences, University of Hyderabad campus, Gachibowli, Hyderabad-500 046, India.
Chem Biol Drug Des. 2010 Jul;76(1):34-42. doi: 10.1111/j.1747-0285.2010.00987.x. Epub 2010 May 4.
Electron transport and respiratory pathways are active in both latent and rapidly growing mycobacteria and remain conserved in all mycobacterial species. In mycobacteria, menaquinone is the sole electron carrier responsible for electron transport. Menaquinone biosynthesis pathway is found to be essential for the growth of mycobacteria. Structural analogs of the substrate or product of this pathway are found to be inhibitory for the growth of Mycobacterium smegmatis and M. tuberculosis. Several plumbagin [5-hydroxy-2-methyl-1, 4-naphthaquinone] derivatives have been analyzed for their inhibitory effects of which butyrate plumbagin was found to be most effective on M. smegmatis mc(2)155, whereas crotonate plumbagin showed greater activity on M. tuberculosis H37Rv. Effect on electron transport and respiration was demonstrated by butyrate plumbagin inhibiting oxygen consumption in M. smegmatis. Structural modifications of these molecules can further be improved upon to generate new molecules against mycobacteria.
电子传递和呼吸途径在潜伏和快速生长的分枝杆菌中均活跃，并且在所有分枝杆菌种中保持保守。在分枝杆菌中，menaquinone 是唯一负责电子传递的电子载体。已发现menaquinone 生物合成途径对分枝杆菌的生长至关重要。该途径的底物或产物的结构类似物被发现对耻垢分枝杆菌和结核分枝杆菌的生长具有抑制作用。已对几种白花丹醌[5-羟基-2-甲基-1,4-萘醌]衍生物进行了分析，以评估其对分枝杆菌的抑制作用，其中丁酸盐白花丹醌对 MC（2）155 表现出最有效的抑制作用，而巴豆酸盐白花丹醌对 H37Rv 表现出更强的活性。丁酸盐白花丹醌抑制分枝杆菌的耗氧量，从而证明了其对电子传递和呼吸的影响。可以进一步对这些分子进行结构修饰，以生成针对分枝杆菌的新型分子。
