Alkaltham Manal Fahad, Almansour Abdulrahman I, Arumugam Natarajan, Vagolu Siva Krishna, Tønjum Tone, Alaqeel Shatha Ibrahim, Rajaratnam Saiswaroop, Sivaramakrishnan Venketesh
Department of Chemistry, College of Science, King Saud University P.O. Box 2455 Riyadh 11451 Saudi Arabia
Department of Microbiology, University of Oslo N-0316 Oslo Norway
RSC Adv. 2024 Apr 11;14(17):11604-11613. doi: 10.1039/d4ra01501k. eCollection 2024 Apr 10.
A new class of structurally intriguing heterocycles embedded with spiropyrrolidine, oxindole and chromanones was prepared by regio- and stereoselectively in quantitative yields using an intermolecular tandem cycloaddition protocol. The compounds synthesized were assayed for their anti-mycobacterial activity against () H37Rv and isoniazid-resistant ( and promoter mutations) clinical isolates. Four compounds exhibited significant antimycobacterial activity against strains tested. In particular, a compound possessing a fluorine substituted derivative displayed potent activity at 0.39 μg mL against H37Rv, while it showed 0.09 μg mL and 0.19 μg mL activity against promoter and mutation isolates, respectively. A molecular docking study was conducted with the potent compound, which showed results that were consistent with the experiments.
通过分子间串联环加成协议,以区域和立体选择性的方式定量制备了一类新的嵌入螺吡咯烷、氧化吲哚和色满酮的结构有趣的杂环化合物。对合成的化合物进行了抗结核分枝杆菌活性测定,针对的是()H37Rv以及耐异烟肼(和启动子突变)的临床分离株。四种化合物对测试的菌株表现出显著的抗结核分枝杆菌活性。特别地,一种具有氟取代衍生物的化合物对H37Rv在0.39μg/mL时显示出强效活性,而对启动子和突变分离株分别显示出0.09μg/mL和0.19μg/mL的活性。对该强效化合物进行了分子对接研究,结果与实验结果一致。