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Synthesis and cytotoxic evaluation of halogenated furanones
Monatshefte für Chemie - Chemical Monthly ( IF 1.7 ) Pub Date : 2020-11-05 , DOI: 10.1007/s00706-020-02708-0
Víctor A. Castro-Torres , Nadia J. Jacobo-Herrera , Lidia Díaz-Sánchez , Leticia Rocha-Zavaleta , Patricia García-López , Mariano Martínez-Vázquez

Abstract

The objective of the current study is to evaluate the potency of halogen-furan-2(5H)-one-type derivatives against human cancer cell lines. Four known bromofuran-2(5H)-one-type derivatives, as well as five new and two known bromo-4-(phenylamino)furan-2(5H)-one-type compounds and six novel and two known halogen-4-alkyl-5-phenyl-3-(phenylamino)furan-2(5H)-one-type derivatives, were synthesized and evaluated for their anticancer activity against prostate (PC-3) and colon (HCT-116) human cancer cell lines. The results showed that only the bromofuran-2(5H)-ones were cytotoxic in both cell lines. Three of these displayed particularly useful antiproliferative activities, in both cancer cells evaluated. (E)-5-(Bromomethylene)furan-2-(5H)-one was the most active against PC-3 (IC50 0.93 ± 0.02 μM) while 3,4-dibromofuran-2(5H)-one was the most active against HCT-116 (IC50 0.4 ± 0.04 μM). Furthermore, flow cytometry studies revealed that the bromofuran-2(5H)-ones induced cell death by apoptosis. Also, it was found that the cytotoxic furanones induced lipid peroxidation, determined by TBARS assay. Thus, cytotoxicity of the active compounds could be associated with ROS production. Additionally, it must be taken into account that all cytotoxic compounds contain an electrophilic carbon atom in position 4, which can explain, through a non-specific reactivity with nucleophiles, the cytotoxic activity of these compounds.

Graphic abstract



中文翻译:

卤代呋喃酮的合成及细胞毒性评价

摘要

本研究的目的是评估卤素呋喃2(5 H)一型衍生物对人类癌细胞系的效力。四种已知的bromofuran-2(5 H)-一型衍生物,以及五种新的和两种已知的bromo-4-(phenylamino)furan-2(5 H)-一型化合物以及六种新颖的和两种已知的卤素-合成了4-烷基-5-苯基-3-(苯基氨基)呋喃-2(5 H)-型衍生物,并评估了其对前列腺癌(PC-3)和结肠癌(HCT-116)的抗癌活性细胞系。结果显示在两种细胞系中仅溴呋喃-2(5 H)-1具有细胞毒性。在评估的两个癌细胞中,其中三个显示出特别有用的抗增殖活性。(E)-5-(溴亚甲基)呋喃-2-(5 H)-一对PC-3活性最高(IC 50 0.93±0.02μM),而3,4-二溴呋喃2(5 H)-一对HCT-116最具活性(IC 50 0.4±0.04μM)。此外,流式细胞仪研究表明,bromofuran-2(5 H)-通过凋亡诱导细胞死亡。另外,还发现通过TBARS测定法确定的细胞毒性呋喃酮诱导脂质过氧化。因此,活性化合物的细胞毒性可能与ROS的产生有关。另外,必须考虑到所有细胞毒性化合物在位置4处都含有一个亲电子碳原子,这可以通过与亲核试剂的非特异性反应来解释这些化合物的细胞毒性活性。

图形摘要

更新日期:2020-11-06
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