Abstract
The fortuitous modification of a quinoline-proline-piperazine side chain linked to a steroid in the presence of lithium (trimethylsilyl) acetylide has generated an unknown product that is more active than its precursor. After having characterized two β-enaminones (two-carbon homologation compounds) that were generated from a simplified model side chain, we have identified the unknown product as being the β-enaminone steroid derivative 1. NMR analysis, especially two-dimensional (2D) experiments (correlation spectroscopy (COSY), NOE spectroscopy (NOESY), heteronuclear single-quantum correlation (HSQC) and heteronuclear multiple-bond correlation (HMBC)) provided crucial information that was found essential in the characterization of enaminone 1. We also proposed a mechanism to rationalize the formation of this biologically active compound.
Highlights
Cancer is still a major cause of death worldwide [1,2]
Steroid derivatives having a (1-quinolin-2-ylcarbonyl)-L-proline-piperazine side chain at position C2 of estra-1,3,5(10)-trien-3,17β-diol [5] or 5α-androstane-3α,17β-diol [6,7,8] represent a new family of anticancer agents. They were found to reduce the proliferation of various human cancer cell lines [8,9,10], as well as to block tumor growth when tested in mouse tumor models of human cancers [7,11]
Fcionmalplyo,uanndin(teexrceisttaitniognobλsmearxva=ti4o1n0isntmhe; estmroisnsgioflnuλomreaxsc=e4n9c4e nomf t)h, iws huinckhnsouwpnpocrotms apomuonddif(iecxactiiotantioofnthλemasxid=e4c1h0ainnmth; eamt iisslsiinokneλdmtaox t=he49s4tenromid), wnuhcilcehussu. pports a modification of the side chain that is linked to the steroid nucleus
Summary
Cancer is still a major cause of death worldwide [1,2]. It is urgent to develop new molecules to counter the uncontrolled proliferation of cancer cells [3,4]. Steroid derivatives having a (1-quinolin-2-ylcarbonyl)-L-proline-piperazine side chain at position C2 of estra-1,3,5(10)-trien-3,17β-diol [5] or 5α-androstane-3α,17β-diol [6,7,8] represent a new family of anticancer agents. They were found to reduce the proliferation of various human cancer cell lines [8,9,10], as well as to block tumor growth when tested in mouse tumor (xenografts) models of human cancers (pancreas, ovary, breast, and leukemia) [7,11].
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