• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
XU Meng, GE Zhixin, HAO Meixi, ZHANG Can. Synthesis and in vitro biological activity of 3-phenyl-3-pyrrolylpentane derivatives[J]. Journal of China Pharmaceutical University, 2016, 47(1): 30-37. DOI: 10.11665/j.issn.1000-5048.20160104
Citation: XU Meng, GE Zhixin, HAO Meixi, ZHANG Can. Synthesis and in vitro biological activity of 3-phenyl-3-pyrrolylpentane derivatives[J]. Journal of China Pharmaceutical University, 2016, 47(1): 30-37. DOI: 10.11665/j.issn.1000-5048.20160104
shu

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

More Information
    Graphical Abstract
    • 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.
    • FullText(HTML)
    • References (11)
  • [1]
    Haussler MR,Whitfield GK,Kaneko I,et al.Molecular mechanisms of vitamin D action[J].Calcif Tissue Int,2013,92(2):77-98.
    [2]
    Bikle DD.Vitamin D metabolism,mechanism of action,and clinical applications[J].Chem Biol,2014,21(3):319-329.
    [3]
    Feldman D,Krishnan AV,Swami S,et al.The role of vitamin D in reducing cancer risk and progression[J].Nat Rev Cancer,2014,14(5):342-357.
    [4]
    Deeb KK,Trump DL,Johnson CS.Vitamin D signalling pathways in cancer:potential for anticancertherapeutics[J].Nat Rev Cancer,2007,7(9):684-700.
    [5]
    Yamada S,Makishima M.Structure-activity relationship of nonsecosteroidal vitamin D receptormodulators[J].Trends Pharmacol Sci,2014,35(7):324-337.
    [6]
    Boehm MF, Fitzgerald P, Zou A, et al. Novel nonsecosteroidal vitamin D mimics exert VDR-modulating activities with less calcium mobilization than 1,25-dihydroxyvitamin D3[J].Chem Biol,1999,6(5):265-275.
    [7]
    Konno K,Maki S,Fujishima T,et al.A novel and practical route to A-ring enyne synthon for 1 alpha,25-dihydroxyvitamin D3 analogs:synthesis of A-ring diastereomers of 1 alpha,25-dihydroxyvitamin D2 and 3-methyl-1,25-dihydroxyvitamin D3[J].Bioorg Med Chem Lett,1998,8(2):151-156.
    [8]
    Ciesielski F, Sato Y, Chebaro Y, et al. Structural basis for the accommodation of bis- and tris-aromatic derivatives in vitamin D nuclear receptor[J].J Med Chem,2012,55(19):8440-8449.
    [9]
    Shen W,Xue J,Zhao Z,et al.Novel nonsecosteroidal VDR agonists with phenyl-pyrrolyl pentaneskeleton[J].Eur J Med Chem,2013,69:768-778.
    [10]
    Garay E, Donnelly R, Wang X, et al. Resistance to 1,25D-induced differentiation in human acute myeloid leukemia HL60-40AF cells is associated with reduced transcriptional activity and nuclear localization of the vitamin D receptor[J].J Cell Physiol,2007,213(3):816-825.
    [11]
    Akhter J,Lu Y,Finlay I,et al.1α,25-Dihydroxyvitamin D 3 and its analogues,EB1089 and CB1093,profoundly inhibit the in vitro proliferation of the human hepatoblastoma cell line HepG2[J].ANZ J Surg,2001,71(7):414-417.
    • Related Articles

  • Related Articles

    [1]SHANG Feiyang, LIU Chengbo, TAN Hongzhou, HE Bing, HE Liqin. Design, synthesis and antiplatelet aggregation activity of 3-acetyl-7-hydroxycoumarin derivatives[J]. Journal of China Pharmaceutical University, 2024, 55(3): 367-374. DOI: 10.11665/j.issn.1000-5048.2023072901
    [2]DAI Weiguo, TAN Hongzhou, GU Hongxia, HE Bing, HE Liqin, HUANG Peng. Design, synthesis and anti-platelet aggregation activity of paeonol oxime derivatives[J]. Journal of China Pharmaceutical University, 2022, 53(5): 535-541. DOI: 10.11665/j.issn.1000-5048.20220504
    [3]WANG Xiaoli, WANG Zhaoya, WANG Linna, JI Hui, ZHANG Yihua, YIN Jian. Design, synthesis and evaluation of hydrogen sulfide-releasing derivatives of ring opening 3-n-butylphthalide as novel platelet aggregation inhibitors[J]. Journal of China Pharmaceutical University, 2016, 47(2): 158-162. DOI: 10.11665/j.issn.1000-5048.20160205
    [4]FANG Jiangen, WANG Xuliang, LING Jingjing, YIN Wei, XU Jinyi, JI Hui, ZHANG Yihua. Synthesis and antiplatelet aggregation/antioxidant activity of 3-alkyl-benzo［c］ selenophen-1(3H)-ones[J]. Journal of China Pharmaceutical University, 2015, 46(5): 552-555. DOI: 10.11665/j.issn.1000-5048.20150506
    [5]WU Mingming, FANG Lei, GOU Shaohua, CHEN Li. 以2-甲基-2-取代苯氧基丙酸为离去基团的铂(Ⅱ)配合物的合成、表征及细胞毒活性[J]. Journal of China Pharmaceutical University, 2013, 44(4): 303-306. DOI: 10.11665/j.issn.1000-5048.20130403
    [6]YANG Chunyu, HUANG Zhangjian, LING Jingjing, JI Hui, LAI Yisheng, XU Jinyi, PENG Sixun, ZHANG Yihua. Synthesis and evaluation of carbamate-isosorbide-3-n-butylphthalide ring opening derivative trihybrids as novel platelet aggregation inhibitors[J]. Journal of China Pharmaceutical University, 2013, 44(3): 202-206. DOI: 10.11665/j.issn.1000-5048.20130302
    [7]ZHANG Bo-yu, SHAN Jia-qi, LIU Lin, JIAO Bo, SUN Hong-bin. Synthesis and antiplatelet aggregation activities of prasugrel derivatives[J]. Journal of China Pharmaceutical University, 2011, 42(4): 305-309.
    [8]Synthesis and anti-platelet aggregation activity of substituted (E)-1，2-diarylethene compounds[J]. Journal of China Pharmaceutical University, 2010, 41(5): 419-423.
    [9]LI Bao-quan, LI Nian-guang, FENG Feng, TANG Yu-ping, DUAN Jin-ao. Synthesis and anti-platelet aggregation activities of ferulic acid esters[J]. Journal of China Pharmaceutical University, 2009, 40(6): 486-490.
    [10]Synthesis and Antiplatelet Aggregation of N Acylated Tetrahydrobenzylisoquinoline[J]. Journal of China Pharmaceutical University, 1997, (5): 3+6-7.

Catalog

    Get Citation
    PDF
    XML
    Article views (1432) PDF downloads (1998) Cited by()
    Turn off MathJax
    Article Contents
    Abstract
    References
    Related Articles

    Copyright © Journal of China Pharmaceutical University苏ICP备12050101号-2

    Address：24 Tongjia Lane, Nanjing City, Jiangsu Province （210009）Tel: 025-83271566E-mail: xuebao@cpu.edu.cn

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    Total visits：308650

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return