3-苯基-3-吡咯基戊烷类化合物的合成及体外生物活性

许梦; 葛执信; 郝玫茜; 张灿

doi:10.11665/j.issn.1000-5048.20160104

3-苯基-3-吡咯基戊烷类化合物的合成及体外生物活性

中国药科大学新药研究中心，江苏省代谢性疾病药物重点实验室

基金项目: 国家自然科学基金资助项目(No.81273468)

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- 刊出日期: 2016-02-24

Synthesis and in vitro biological activity of 3-phenyl-3-pyrrolylpentane derivatives

摘要

摘要: 以非开环甾体类维生素D受体(VDR)激动剂LG190155为先导物，通过结构改造设计合成了一系列3-苯基-3-吡咯基戊烷类化合物。通过测定目标化合物对HL-60细胞的促分化能力间接测定其对VDR的激动能力。结果表明，化合物 13a ， 13c ， 13d ， 13h ， 13i，13j 表现出较好的HL-60促分化活性(EC₅₀<；50 μmol/L)，提示这6个化合物具有较好的VDR激动能力。其中以化合物 13j 的促分化活性最高(EC₅₀=0.10 μmol/L)，且优于先导化合物LG190155。采用MTT法评价目标化合物对VDR高表达的肿瘤细胞(人前列腺癌细胞PC-3、人乳腺癌细胞MCF-7、人结肠癌细胞Caco-2、人肝癌细胞HepG2)和人肝正常细胞(L02)的增殖抑制活性。结果表明，化合物 13a 在HepG2细胞株中的增殖抑制活性最好(IC₅₀=0.11 μmol/L)，且对普通肝细胞L02的抑制作用较低(IC₅₀=15.24 μmol/L)，说明化合物 13a 对肝肿瘤细胞具有一定选择性。此外还发现所合成化合物的促分化活性与抑制增殖活性成正相关。
- 3-苯基-3-吡咯基戊烷衍生物 /
- 非开环甾体类激动剂 /
- 合成 /
- 维生素D受体激动活性 /
- 肿瘤 /
- 增殖抑制
Abstract: A new series of 3-phenyl-3-pyrrolylpentane derivatives were synthesized through modifying the structure of the lead compound LG19055, which has been the first nonsecosteroidal vitamin D receptor(VDR)agonist reported. The VDR-agonistic ability of target compounds was measured indirectly by evaluating the differentiation ability of HL-60 cell. The results showed that compounds 13a , 13c , 13d , 13h , 13i , 13j had excellent VDR-agonistic ability(EC₅₀< 50 μmol/L), especially for compound 13j (EC₅₀=0. 10 μmol/L), which was more potential than that of lead compound LG190155. Their proliferation inhibitory activities in vitro were evaluated by MTT assay in MCF-7, PC-3, Caco-2, HepG2 and L02 cell lines. Compound 13a exhibited significant inhibitory effects on HepG2 cell line(IC₅₀=0. 11 μmol/L)。Moreover, the inhibitory effect of compound 13a on non-tumor liver L02 cell line was relatively weak(IC₅₀=15. 24 μmol/L), suggesting that compound 13a had selective inhibitory effects on liver cancer cells. Additionally, HL-60 cell differentiation-inducing activity and the inhibitory effect of cancer cells were positively related.
- 3-phenyl-3-pyrrolylpentane derivatives /
- nonsecosteroidal agonist /
- synthesis /
- VDR-agonistic ability /
- tumor /
- proliferation inhibition

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参考文献(11)

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文章访问数: 1440
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3-苯基-3-吡咯基戊烷类化合物的合成及体外生物活性

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出版历程

Synthesis and in vitro biological activity of 3-phenyl-3-pyrrolylpentane derivatives

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出版历程

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