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Synthesis and Antitumor Evaluation of Novel Hybrids of Phenylsulfonylfuroxan and Estradiol Derivatives |
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| Authors: | Qi Wan Yan Deng Yaoqing Huang Zhihui Yu Chunli Wang Ke Wang Assoc Prof Jibin Dong Prof Ying Chen |
| Institution: | 1. Department of Medicinal Chemistry School of Pharmacy, Fudan University, 826, Zhangheng Road, Shanghai, China
Q. W. and Y. D. are co-first-authors and contributed equally to this work.;2. Department of Pharmacology and Biochemistry School of Pharmacy, Fudan University, 826, Zhangheng Road, Shanghai, China Q. W. and Y. D. are co-first-authors and contributed equally to this work.;3. Department of Medicinal Chemistry School of Pharmacy, Fudan University, 826, Zhangheng Road, Shanghai, China;4. Department of Pharmacology and Biochemistry School of Pharmacy, Fudan University, 826, Zhangheng Road, Shanghai, China |
| Abstract: | 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. |
| Keywords: | apoptosis estradiol nitric oxide furoxan derivatives anticancer drugs |