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Design, stereoselective synthesis and anticancer efficacy of a new class of functionalized pyrrolizidine heterocyclic hybrids
Journal of King Saud University-Science ( IF 3.8 ) Pub Date : 2023-11-22 , DOI: 10.1016/j.jksus.2023.103009
Raju Suresh Kumar , Dhaifallah M. Al-thamili , Khloud Ibrahim Al-Shemaimari , Faruq Mohammad , Mohamad Altaf , Rashid Ayub

Eight new functionalized spirooxindole-pyrrolizidine heterocyclic hybrids has been obtained from N-pyridinylmethyl-bisarylmethylidene-pyridinones, Isatin and L-Proline by a multi-component cycloaddition reaction. Such synthesized derivatives are being characterized systematically with the aid of instrumental facilities like FT-IR, NMR spectroscopy, and Mass spectrometry. Following this, all the compounds are tested for the anticancer potentials in vitro using HepG2 cells (cancer cells). The compound with no substitution on the aryl rings (phenyl rings), displayed the highest activity among the spirooxindole-pyrrolizidines. Further the most active heterocyclic hybrids are verified for toxicity effects against L929 cells (non-cancer cells; at 200 µg/mL for 24 h). Finally, the cell viability losses for these most active compounds (at its IC50 value) are addressed by assaying the activity of free radicals, apoptosis, and caspases.



中文翻译:

一类新型功能化吡咯里西啶杂环杂化物的设计、立体选择性合成及其抗癌功效

通过多组分环加成反应,从N-吡啶基甲基-双芳基亚甲基-吡啶酮、靛红和 L-脯氨酸获得了八种新的功能化螺吲哚-吡咯里西啶杂环杂化物。借助 FT-IR、NMR 光谱和质谱等仪器设施,可以对此类合成衍生物进行系统表征。此后,所有化合物均使用 HepG2 细胞(癌细胞)进行体外抗癌潜力测试。芳环(苯环)上没有取代的化合物在螺吲哚-吡咯里西啶中表现出最高的活性。此外,还验证了最活跃的杂环杂合体对 L929 细胞(非癌细胞;200 µg/mL,24 小时)的毒性作用。最后,通过测定自由基、细胞凋亡和半胱天冬酶的活性来解决这些最具活性的化合物(以其 IC 50值)的细胞活力损失。

更新日期:2023-11-22
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