کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1363902 | 981524 | 2008 | 16 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Chemical synthesis of 2β-amino-5α-androstane-3α,17β-diol N-derivatives and their antiproliferative effect on HL-60 human leukemia cells Chemical synthesis of 2β-amino-5α-androstane-3α,17β-diol N-derivatives and their antiproliferative effect on HL-60 human leukemia cells](/preview/png/1363902.png)
Even though few steroids are used for the treatment of leukemia, 2β-(4-methylpiperazinyl)-5α-androstane-3α,17β-diol (1) was recently reported for its ability to inhibit the proliferation of human leukemia HL-60 cells. With an efficient procedure that we had developed for the aminolysis of hindered steroidal epoxides, we synthesized a series of 2β-amino-5α-androstane-3α,17β-diol N-derivatives structurally similar to 1. Hence, the opening of 2,3α-epoxy-5α-androstan-17β-diol with primary and secondary amines allowed the synthesis of aminosteroids with diverse length, ramification, and functionalization of the 2β-side chain. Sixty-four steroid derivatives were tested for their capacity to inhibit the proliferation of HL-60 cells; thus obtaining first structure–activity relationship results. Ten aminosteroids with long alkyl chains (7–16 carbons) or bulky groups (diphenyl or adamantyl) have shown antiproliferative activity over 78% at 10 μM and superior to that of the lead compound. The 3,3-diphenylpropylamino, 4-nonylpiperazinyl and octylamino derivatives of 5α-androstane-3α,17β-diol inhibited the HL-60 cell growth with IC50 of 3.1, 4.2 and 6.4 μM, respectively. They were also found to induce the HL-60 cell differentiation.
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Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 9, 1 May 2008, Pages 5062–5077