Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 32 Vavilov St., 119991 Moscow, Russia.
Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, 47 Leninsky Avenue, 119991 Moscow, Russia.
Molecules. 2023 Apr 19;28(8):3568. doi: 10.3390/molecules28083568.
Bacterial cystathionine γ-lyase (bCSE) is the main producer of HS in pathogenic bacteria such as , , etc. The suppression of bCSE activity considerably enhances the sensitivity of bacteria to antibiotics. Convenient methods for the efficient synthesis of gram quantities of two selective indole-based bCSE inhibitors, namely (2-(6-bromo-1-indol-1-yl)acetyl)glycine (NL1), 5-((6-bromo-1-indol-1-yl)methyl)- 2-methylfuran-3-carboxylic acid (NL2), as well as a synthetic method for preparation 3-((6-(7-chlorobenzo[]thiophen-2-yl)-1-indol-1-yl)methyl)- 1-pyrazole-5-carboxylic acid (NL3), have been developed. The syntheses are based on the use of 6-bromoindole as the main building block for all three inhibitors (NL1, NL2, and NL3), and the designed residues are assembled at the nitrogen atom of the 6-bromoindole core or by the substitution of the bromine atom in the case of NL3 using Pd-catalyzed cross-coupling. The developed and refined synthetic methods would be significant for the further biological screening of NL-series bCSE inhibitors and their derivatives.
细菌胱硫醚γ-裂解酶（bCSE）是病原体如 、 等细菌中 HS 的主要产生者。抑制 bCSE 活性可显著提高细菌对抗生素的敏感性。方便的方法可高效合成两种选择性吲哚基 bCSE 抑制剂，即（2-（6-溴-1-吲哚-1-基）乙酰基）甘氨酸（NL1）和 5-（（6-溴-1-吲哚-1-基）甲基）-2-甲基呋喃-3-羧酸（NL2），以及合成 3-（（6-（7-氯苯并噻吩-2-基）-1-吲哚-1-基）甲基）-1-吡唑-5-羧酸（NL3）的方法。这些合成方法基于使用 6-溴吲哚作为三种抑制剂（NL1、NL2 和 NL3）的主要构建块，并且设计的残基在 6-溴吲哚核的氮原子上组装，或者在 NL3 的情况下通过钯催化的交叉偶联取代溴原子。开发和完善的合成方法对于进一步的 NL 系列 bCSE 抑制剂及其衍生物的生物学筛选具有重要意义。
