- Synthesis and evaluation of Na+/K+-ATP-ase inhibiting and cytotoxic in vitro activities of oleandrigenin and its selected 17β-(butenolidyl)- and 17β-(3-furyl)- analogues
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Natural cardiac-active principles built upon the 14,16β-dihydroxy-5β,14β-androstane core and bearing a heterocyclic substituent at 17β, in particular, a cardenolide - oleandrin and a bufadienolide - bufotalin, are receiving a great deal of attention as potential anticancer drugs. The densely substituted and sterically shielded ring D is the particular structural feature of these compounds. The first synthesis of oleandrigenin from easily available steroid starting material is reported here. Furthermore, selected 17β-(4-butenolidyl)- and 17β-(3-furyl)-14,16β-dihydroxy-androstane derivatives were en route synthesized and examined for their Na+/K+-ATP-ase inhibitory properties as well as cytotoxic activities in normal and cancer cell lines. It was found that the furyl-analogue of oleandrigenin/bufatalin (7) and some related 17-(3-furyl)- derivatives (19, 21) show remarkably high Na+/K+-ATP-ase inhibitory activity as well as significant cytotoxicity in vitro. In addition, oleandrigenin 2 compared to derivatives 21 and 25 induced strong apoptosis in human cervical carcinoma HeLa cells after 24 h of treatment.
- ?tenclová, Tereza,Kubala, Martin,Michalak, Karol,Rárová, Lucie,Strnad, Miroslav,Wicha, Jerzy
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- SYNTHESIS AND BIOLOGICAL ACTIVITY OF SOME CARDIOTONIC COMPOUNDS RELATED TO GITOXIGENIN
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The four diastereomeric 3,16-diacetates 6, 9, 10 and 11 were prepared from gitoxin 1 by the routes shown in Schemes 1 and 2 and tested for inotropic activity in the isolated guinea-pig atrial preparation.In line with earlier findings in the digitoxigenin series, derivatives with a 3α-acetoxy function, viz 9 and 10, possessed high biological activity.
- Humber, David C.,Jones, Paul S.,Phillipps, Gordon H.
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- Synthesis of Cardiotonic Steroids Oleandrigenin and Rhodexin B
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This article describes a concise synthesis of cardiotonic steroids oleandrigenin (7) and its subsequent elaboration into the natural product rhodexin B (2) from the readily available intermediate (8) that could be derived from the commercially available steroids testosterone or DHEA via three-step sequences. These studies feature an expedient installation of the β16-oxidation based on β14-hydroxyl-directed epoxidation and subsequent epoxide rearrangement. The following singlet oxygen oxidation of the C17 furan moiety provides access to oleandrigenin (7) in 12 steps (LLS) and a 3.1% overall yield from 8. The synthetic oleandrigenin (7) was successfully glycosylated with l-rhamnopyranoside-based donor 28 using a Pd(II)-catalyst, and the subsequent deprotection under acidic conditions provided cytotoxic natural product rhodexin B (2) in a 66% yield (two steps).
- Fejedelem, Zachary,Carney, Nolan,Nagorny, Pavel
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p. 10249 - 10262
(2021/07/31)
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- Succinates and maleates of some cardenolides, and their potassium salts
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The succinates of corotoxigenin, digitoxigenin, and oleandrigenin, and the maleate of strophanthidin, and their potassium salts, have been synthesized. In contrast to the initial cardenolides (1, 4, 7, and 10), the succinates (2, 5, and 8) and the maleate (11) and their potassium salts (3, 6, 9, and 12) possess no cardiotonic activity.
- Komissarenko,Komissarenko,Derkach
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p. 553 - 556
(2007/10/03)
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- Cardiac Glycosides. 6. Gitoxigenin C16 Acetates, Formates, Methoxycarbonates, and Digitoxosides. Synthesis and Na+, K+ -ATPase Inhibitory Activities
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A series of 17 gitoxigenin 16β-formates, acetates, and methoxycarbonates was synthesized, including their 3β-acetates, formates, and digitoxosides.A 16β-formate group was generally found to increase activity 30 times, a 16β-acetate group 9-12 times, while a 16β-methoxycarbonate decreased activity by two-thirds. 3β-Formates and acetates had little effect on activity by themselves, but sometimes reduced the activity-increasing properties of 16β-formates and acetates.A 3β-digitoxoside increases the activity of ditoxigenin by 15 times, but the effect is less ifthe 16β-group is esterified.And finally, a 16-one decreases activity dramatically.These data suggest an important role for C16 esters and possibly the presence of a separate binding site on Na+, K+ -ATPase corresponding to the cardenolide C16 position.
- Hashimoto, Toshihiro,Rathore, Hargovind,Satoh, Daisuke,Hong, George,Griffin, Jane F.,et al.
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p. 997 - 1003
(2007/10/02)
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