Synthesis, NMR Characterization, and Antileukemic Activity of <i>N</i>-Nonanoylpiperazinyl-5α-Androstane-3α,17β-Diol A-Ring Derivatives
The combination of an androstane-3,17-diol nucleus and a 2β-<i>N</i>-alkylamidopiperazino sidechain is important for the anticancer activity of a new family of steroid derivatives. As the structure-activity relationship studies have so far been limited to the beta orientation of the subs...
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MDPI AG
2020-12-01
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| Series: | Magnetochemistry |
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| Online Access: | https://www.mdpi.com/2312-7481/7/1/3 |
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| author | Donald Poirier Imad Raad Jenny Roy René Maltais |
| author_facet | Donald Poirier Imad Raad Jenny Roy René Maltais |
| author_sort | Donald Poirier |
| collection | DOAJ |
| description | The combination of an androstane-3,17-diol nucleus and a 2β-<i>N</i>-alkylamidopiperazino sidechain is important for the anticancer activity of a new family of steroid derivatives. As the structure-activity relationship studies have so far been limited to the beta orientation of the substituent at position 2 of the steroid nucleus, a series of analogs (compounds <b>1</b>–<b>4</b>) were synthesized to investigate the impact on biological activity of A-ring substitution. Nuclear magnetic resonance (NMR) analysis, especially using a series of 2D experiments, such as correlation spectroscopy (COSY), homonuclear Overhauser effect spectroscopy (NOESY), heteronuclear single-quantum correlation (HSQC), and heteronuclear multiple-bond correlation (HMBC) provided crucial information that was found essential in confirming the sidechain position and orientation of compounds <b>1</b>–<b>4</b>. Assessment of their antiproliferative activity on leukemia HL-60 cells confirmed the best efficiency of the 2β-sidechain/3α-OH orientation (compound <b>1</b>) compared to the other configurations tested (compounds <b>2</b>–<b>4</b>). |
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| institution | Directory Open Access Journal |
| issn | 2312-7481 |
| language | English |
| last_indexed | 2024-03-10T13:50:05Z |
| publishDate | 2020-12-01 |
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| series | Magnetochemistry |
| spelling | doaj.art-1ec5a7ea7c204053ba1accac54b67f7f2023-11-21T02:09:41ZengMDPI AGMagnetochemistry2312-74812020-12-0171310.3390/magnetochemistry7010003Synthesis, NMR Characterization, and Antileukemic Activity of <i>N</i>-Nonanoylpiperazinyl-5α-Androstane-3α,17β-Diol A-Ring DerivativesDonald Poirier0Imad Raad1Jenny Roy2René Maltais3Laboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de Québec—Research Center, Québec, QC G1V 4G2, CanadaLaboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de Québec—Research Center, Québec, QC G1V 4G2, CanadaLaboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de Québec—Research Center, Québec, QC G1V 4G2, CanadaLaboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de Québec—Research Center, Québec, QC G1V 4G2, CanadaThe combination of an androstane-3,17-diol nucleus and a 2β-<i>N</i>-alkylamidopiperazino sidechain is important for the anticancer activity of a new family of steroid derivatives. As the structure-activity relationship studies have so far been limited to the beta orientation of the substituent at position 2 of the steroid nucleus, a series of analogs (compounds <b>1</b>–<b>4</b>) were synthesized to investigate the impact on biological activity of A-ring substitution. Nuclear magnetic resonance (NMR) analysis, especially using a series of 2D experiments, such as correlation spectroscopy (COSY), homonuclear Overhauser effect spectroscopy (NOESY), heteronuclear single-quantum correlation (HSQC), and heteronuclear multiple-bond correlation (HMBC) provided crucial information that was found essential in confirming the sidechain position and orientation of compounds <b>1</b>–<b>4</b>. Assessment of their antiproliferative activity on leukemia HL-60 cells confirmed the best efficiency of the 2β-sidechain/3α-OH orientation (compound <b>1</b>) compared to the other configurations tested (compounds <b>2</b>–<b>4</b>).https://www.mdpi.com/2312-7481/7/1/3steroidandrostanenuclear magnetic resonanceantileukemic agentHL-60 cells |
| spellingShingle | Donald Poirier Imad Raad Jenny Roy René Maltais Synthesis, NMR Characterization, and Antileukemic Activity of <i>N</i>-Nonanoylpiperazinyl-5α-Androstane-3α,17β-Diol A-Ring Derivatives Magnetochemistry steroid androstane nuclear magnetic resonance antileukemic agent HL-60 cells |
| title | Synthesis, NMR Characterization, and Antileukemic Activity of <i>N</i>-Nonanoylpiperazinyl-5α-Androstane-3α,17β-Diol A-Ring Derivatives |
| title_full | Synthesis, NMR Characterization, and Antileukemic Activity of <i>N</i>-Nonanoylpiperazinyl-5α-Androstane-3α,17β-Diol A-Ring Derivatives |
| title_fullStr | Synthesis, NMR Characterization, and Antileukemic Activity of <i>N</i>-Nonanoylpiperazinyl-5α-Androstane-3α,17β-Diol A-Ring Derivatives |
| title_full_unstemmed | Synthesis, NMR Characterization, and Antileukemic Activity of <i>N</i>-Nonanoylpiperazinyl-5α-Androstane-3α,17β-Diol A-Ring Derivatives |
| title_short | Synthesis, NMR Characterization, and Antileukemic Activity of <i>N</i>-Nonanoylpiperazinyl-5α-Androstane-3α,17β-Diol A-Ring Derivatives |
| title_sort | synthesis nmr characterization and antileukemic activity of i n i nonanoylpiperazinyl 5α androstane 3α 17β diol a ring derivatives |
| topic | steroid androstane nuclear magnetic resonance antileukemic agent HL-60 cells |
| url | https://www.mdpi.com/2312-7481/7/1/3 |
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