First lepidiline-inspired 1,3-dibenzyl 2-CF3S-imidazoliums: Design, synthesis and cytotoxic activity study

IF 7.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy Pub Date : 2025-09-29 DOI:10.1016/j.biopha.2025.118606

Wiktor K. Poper , Marta Denel-Bobrowska , Agnieszka B. Olejniczak , Marcin Jasiński

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引用次数: 0

Abstract

A series of lepidiline-type 4,5-dimethylimidazolium hexafluorophosphates, functionalized with F atom(s) as well as the CF₃, OCF₃, OCH₃ and SCF₃ groups located either in the central core or placed at benzyl-type N-substituents, was prepared, and the cytotoxicity against selected cancer cell lines was examined. The applied four-step protocol based on condensation of diacetyl monoxime with formaldimines (hexahydro-1,3,5-triazines), one-pot telescopic sulfur-transfer followed by electrophilic trifluoromethylation, and subsequent N-alkylation of the central imidazole ring, enabled access to symmetrical and unsymmetrical products. The counterion metathesis provided crystalline hexafluorophosphates, which were isolated in high overall yield. Analysis of biological activity of the intermediate CF₃S-imidazoles and the corresponding imidazoliums against HeLa, HepG2, and A549 cancer cell lines revealed amplified cytotoxicity of the final salts in comparison to natural lepidiline alkaloids, which is promising in the context of drug discovery.

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首个以氯吡啶为灵感的1,3-二苄基2- cf3s -咪唑：设计、合成和细胞毒性活性研究。

制备了一系列由F原子、CF3、OCF3、OCH3和SCF3基团（位于中心核或位于苄基n取代基上）功能化的lepidilin型4,5-二甲基咪唑六氟磷酸盐，并检测了它们对选定癌细胞的细胞毒性。所采用的四步工艺是：二乙酰一元肟与甲醛二胺（六氢-1,3,5-三嗪）缩合，一锅伸缩硫转移，然后是亲电三氟甲基化，然后是中心咪唑环的n -烷基化，从而可以得到对称和不对称的产物。反离子复分解制得结晶六氟磷酸盐，总收率较高。对中间体cf3s -咪唑及相应的咪唑类药物对HeLa、HepG2和A549癌细胞的生物活性分析表明，与天然大麻碱相比，最终盐的细胞毒性更强，这在药物开发方面具有广阔的前景。

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来源期刊

Biomedicine & Pharmacotherapy 医学-药学

CiteScore

11.90

自引率

2.70%

发文量

1621

审稿时长

48 days

期刊介绍： Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.