Synthesis of Pregnane Derivatives, Their Cytotoxicity on LNCap and PC-3 Cells, and Screening on 5α-Reductase Inhibitory Activity

Molecules

Sujeong Kim¹ 

[1] College of Pharmacy, Catholic University of Daegu, Hayang, 712-702, Korea

关键词: 5α-reductase inhibitor;    LNCaP;    PC-3;    epoxypregnanes;    20-oxime pregnanes;   

DOI  :  10.3390/molecules14114655

来源: mdpi

【 摘 要 】

A series of epoxy- and/or 20-oxime pregnanes were synthesized from commercially available pregnenolone. Compounds 1, 3, 7, 8 and 11-13 were evaluated for cytotoxicity activity towards LNCaP (androgen-dependent) and PC-3 (androgenindependent) prostate cancer cells. Compound 13 showed the highest activity on both LNCaP (IC₅₀ 15.17 μM) and PC-3 (IC₅₀ 11.83 μM) cell lines. Compound 11 showed weak activity on LNCaP cells (IC₅₀ 71.85 μM) and 8 showed the weak activity on PC-3 cells (IC₅₀ 68.95 μM), respectively. The 5α-reductase II (5AR2) inhibitory effects of compounds 1-3, 5 and 7-13 were investigated in a convenient screening model, in which compounds 5, 8, 11 and 12 were observed to be potential inhibitors of 5α-reductase, in particular, the 4-azasteroid 11, that also inhibited cell proliferation of androgen-dependent cells and 8, that in addition inhibited PC-3 cells more potently than LNCaP cells.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.