Data_sheet_1_Synthesis, Antimicrobial Activity, Structure-Activity Relationship, and Molecular Docking Studies of Indole Diketopiperazine Alkaloids.docx

Strategies for the synthesis of indole diketopiperazine alkaloids (indole DKPs) have been described and involve three analogs of indole DKPs. The antimicrobial activity and structure-activity relationship (SAR) of 24 indole DKPs were explored. Compounds 3b and 3c were found to be the most active, with minimum inhibitory concentrations (MIC) values in the range of 0.94–3.87 μM (0.39–1.56 μg/mL) against the four tested bacteria (Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli). Furthermore, compounds 4a and 4b displayed broad-spectrum antimicrobial activity with MIC values of 1.10–36.9 μM (0.39–12.5 μg/mL) against all tested bacteria and plant pathogenic fungi (Colletotrichum gloeosporioides, Valsa mali, Alternaria alternata and Alternaria brassicae). According to the in silico study, compounds 3c showed significant binding affinity to the FabH protein from Escherichia coli, which has been identified as the key target enzyme of fatty acid synthesis (FAS) in bacteria. Therefore, these compounds are not only promising new antibacterial agents but also potential FabH inhibitors.

本研究报道了吲哚二酮哌嗪类生物碱（indole DKPs）的合成策略，该类化合物涵盖三类吲哚二酮哌嗪类似物。本研究针对24种吲哚二酮哌嗪类化合物的抗菌活性与构效关系（SAR）展开了探究。实验结果显示，化合物3b与3c的抗菌活性最为突出，针对4种受试细菌（金黄色葡萄球菌、枯草芽孢杆菌、铜绿假单胞菌及大肠杆菌）的最低抑菌浓度（MIC）区间为0.94~3.87 μM（0.39~1.56 μg/mL）。此外，化合物4a与4b展现出广谱抗菌活性，对所有受试细菌及植物病原真菌（胶孢炭疽菌、苹果腐烂病菌、链格孢菌、芸苔链格孢菌）的最低抑菌浓度范围为1.10~36.9 μM（0.39~12.5 μg/mL）。经虚拟实验分析，化合物3c可与大肠杆菌的FabH蛋白（FabH protein）产生显著结合亲和力，而该蛋白已被证实为细菌脂肪酸合成（FAS）的关键靶标酶。综上，此类化合物不仅是极具开发潜力的新型抗菌剂，同时也是潜在的FabH抑制剂。