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

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.