Department of Chemistry, College of Science, King Saud University, P.O Box 2455, Riyadh 11451, Saudi Arabia.
Department of Chemistry, College of Science, King Saud University, P.O Box 2455, Riyadh 11451, Saudi Arabia.
J Infect Public Health. 2021 Dec;14(12):1810-1814. doi: 10.1016/j.jiph.2021.10.027. Epub 2021 Nov 4.
Microbial infections together with rising drug resistance pose a threat to immunocompromised individual. In this perspective, compounds with spirooxindolopyrrolidine play a significant role in research on antimicrobial drug delivery research owing to their various pharmaceutical activities. Spiroheterocyclic compounds are present in number of medications as active motif due to their exceptional structural properties which enable for easy interaction with the protein of the biological target. Inspired by this biological precedent encouraged to synthesize a new class of dispirooxindole fused pyrrolidine heterocycles via a three-component cycloaddition strategy.
The new class of structurally intriguing spirooxindolopyrrolidines were synthesized through three component cycloaddition process and the structure of products were assigned through spectroscopic analysis. The newly synthesized compounds were assessed for their antimicrobial sensitivity test with standard Kirby Bauer method with common drugs.
The structurally unexplored hybrid heterocycles fused spirooxindolopyrrolidine exhibited excellent antimicrobial activity against the common nosocomial microbial pathogens. Of four compounds, the compound bearing a chlorine atom on the aryl ring (4a) exhibited significant antimicrobial activity (zone of inhibition: 9.00 ± 1.00-17.00 ± 0.35 mm and MIC: 16.00-256.00 μg/mL) against selected nosocomial infection causing microbial pathogens. Hence, the compound 4a has been considered as an effective drug of interest in therapeutic field for compacting infectious diseases causing pathogens.
With an aim of developing more effective and economically more affordable antimicrobial leads with a unique mechanism of action, we have designed and synthesized structurally diverse spirooxindolopyrrolidine tethered hybrids that has been assayed against multidrug resistant nosocomial pathogens. The regioisomer having chloro substituted on the phenyl ring showed potent activity when compared to standard drug. Future studies are required to explicate the pharmacological properties of new hybrid heterocycles that have been synthesized in our laboratory for the novel therapeutic development.
微生物感染和不断上升的药物耐药性对免疫功能低下的个体构成威胁。在这方面，具有螺噁吲哚并吡咯烷的化合物由于其各种药物活性，在抗菌药物输送研究中发挥着重要作用。由于其特殊的结构特性，螺杂环化合物作为活性基序存在于许多药物中，这使得它们能够与生物靶标蛋白进行轻松相互作用。受此生物学先例的启发，我们鼓励通过三组分环加成策略合成一类新的双螺吲哚并吡咯烷杂环化合物。
通过三组分环加成过程合成了具有结构趣味性的新型螺噁吲哚并吡咯烷，并通过光谱分析确定了产物的结构。通过与常用药物的标准 Kirby Bauer 方法评估新合成化合物的抗菌敏感性测试。
融合螺噁吲哚并吡咯烷的结构未探索的杂合杂环表现出对常见医院感染性微生物病原体的优异抗菌活性。在四种化合物中，带有芳基环上氯原子的化合物（4a）表现出显著的抗菌活性（抑菌圈：9.00 ± 1.00-17.00 ± 0.35 mm 和 MIC：16.00-256.00 μg/mL），对抗选定的引起医院感染的微生物病原体。因此，化合物 4a 被认为是治疗引起传染病的病原体的有效候选药物。
为了开发更有效且在经济上更负担得起的具有独特作用机制的抗菌先导化合物，我们设计并合成了结构多样的螺噁吲哚并吡咯烷连接的杂环，并用其对抗多种耐药性医院病原体进行了测试。与标准药物相比，具有氯取代苯基环的区域异构体表现出更强的活性。需要进一步的研究来阐明我们实验室合成的新型杂环化合物的药理学特性，以便进行新的治疗开发。
