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Synthesis and Antitumor Evaluation of Novel Hybrids of Phenylsulfonylfuroxan and Estradiol Derivatives.
ChemistryOpen ( IF 2.5 ) Pub Date : 2019-12-11 , DOI: 10.1002/open.201900228
Qi Wan 1 , Yan Deng 2 , Yaoqing Huang 1 , Zhihui Yu 1 , Chunli Wang 1 , Ke Wang 1 , Jibin Dong 2 , Ying Chen 1
Affiliation  

Fifteen novel furoxan‐based nitric oxide (NO) releasing hybrids of estradiol derivatives were synthesized and evaluated in vitro anti‐proliferative activity in MDA‐MB‐231, A2780, Hela and HUVEC cell lines. Most of them displayed potent anti‐proliferative effects. Among the compounds, 4‐bromo‐3‐((phenylsulfonyl)‐1,2,5‐oxadiazole 2‐oxide)‐oxy‐propoxy‐estradiol (11 b) exhibited the best activity with IC50 values of 3.58–0.0008 μM. Preliminary pharmacological studies showed that 11 b induced apoptosis and hardly affected the cell cycle of MDA‐MB‐231 cell line. NO‐releasing capacity and inhibition of ERK/MAPK pathway signaling might explain the potent antineoplastic activity of these compounds. The preliminary structure‐activity relationship (SAR) showed that steroidal scaffolds with a linker in 3‐position were favorable moieties to evidently increase the bioactivities of these hybrids. Overall, these results implied that 11 b merited to be further investigated as a promising anti‐cancer candidate.

中文翻译:

苯磺酰呋喃氧星和雌二醇衍生物的新型杂化物的合成和抗肿瘤评价。

合成了 15 种新型基于呋喃酮的一氧化氮 (NO) 释放雌二醇衍生物杂合体,并评估了 MDA-MB-231、A2780、Hela 和 HUVEC 细胞系的体外抗增殖活性。其中大多数表现出有效的抗增殖作用。在这些化合物中,4-溴-3-((苯磺酰基)-1,2,5-恶二唑2-氧化物)-氧基-丙氧基-雌二醇( 11 b )表现出最好的活性,IC 50值为3.58–0.0008 μM。初步药理学研究表明11b诱导细胞凋亡且几乎不影响MDA-MB-231细胞系的细胞周期。NO 释放能力和 ERK/MAPK 通路信号传导的抑制可能解释了这些化合物的有效抗肿瘤活性。初步的构效关系(SAR)表明,3位具有连接基的甾体支架是明显提高这些杂化物生物活性的有利部分。总体而言,这些结果表明11 b作为一种有前途的抗癌候选药物值得进一步研究。
更新日期:2019-12-11
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