Synthesis and in vitro bioIogicaI activity of 3-phenyI-3-pyrroIyIpentane deriva-tives
10.11665/j.issn.1000-5048.20160104
- VernacularTitle:3-苯基-3-吡咯基戊烷类化合物的合成及体外生物活性
- Author:
Meng XU
;
Zhixin GE
;
Meixi HAO
;
Can ZHANG
- Publication Type:Journal Article
- Keywords:
3-phenyl-3-pyrrolylpentane derivatives;
nonsecosteroidal agonist;
synthesis;
VDR-agonistic ability;
tumer;
proliferation inhibition
- From:
Journal of China Pharmaceutical University
2016;(1):30-37
- CountryChina
- Language:Chinese
-
Abstract:
A new series of 3-phenyl-3-pyrrolylpentane derivatives are synthesized through modifying the structure of lead compound LG19055,a nonsecosteroidal vitamin D receptor(VDR)agonist.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 have 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 =0.11μmol /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 has selective inhibitory effects on liver cancer cells.Additionally,HL-60 cell differentiation-inducing activity and the inhibitory effect of cancer cells were posi-tively related.
