Synthesis and biological activities of turkesterone 11?-acyl derivatives
Turkesterone is a phytoecdysteroid possessing an 11alpha-hydroxyl group. It is an analogue of the insect steroid hormone 20-hydroxyecdysone. Previous ecdysteroid QSAR and molecular modelling studies predicted that the cavity of the ligand-binding domain of the ecdysteroid receptor would possess spac...
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doaj-1c25cb13d4e54e3facef6f786beccff52020-11-24T20:43:54ZengOxford University PressJournal of Insect Science1536-24422003-02-0136Synthesis and biological activities of turkesterone 11?-acyl derivativesLaurence DinanPauline BournePensri WhitingAda TsitsekliZiyadilla SaatovTarlochan S. DhadiallaRobert E. HormannRené LafontJosep CollTurkesterone is a phytoecdysteroid possessing an 11alpha-hydroxyl group. It is an analogue of the insect steroid hormone 20-hydroxyecdysone. Previous ecdysteroid QSAR and molecular modelling studies predicted that the cavity of the ligand-binding domain of the ecdysteroid receptor would possess space in the vicinity of C-11/C-12 of the ecdysteroid. We report the regioselective synthesis of a series of turkesterone 11alpha-acyl derivatives in order to explore this possibility. The structures of the analogues have been unambiguously determined by spectroscopic means (NMR and low-resolution mass spectrometry). Purity was verified by HPLC. Biological activities have been determined in Drosophila melanogaster BII cell-based bioassay for ecdysteroid agonists and in an in vitro radioligand-displacement assay using bacterially expressed D. melanogaster EcR/USP receptor proteins. The 11alpha-acyl derivatives do retain a significant amount of biological activity relative to the parent ecdysteroid. Further, although activity initially drops with the extension of the acyl chain length (C2 to C4), it then increases (C6 to C10), before decreasing again (C14 and C20). The implications of these findings for the interaction of ecdysteroids with the ecdysteroid receptor and potential applications in the generation of affinity-labelled and fluorescently-tagged ecdysteroids are discussed.http://www.insectscience.org/3.6/steroidecdysteroid20-hydroxecdysoneQSARsteroid hormone receptor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laurence Dinan Pauline Bourne Pensri Whiting Ada Tsitsekli Ziyadilla Saatov Tarlochan S. Dhadialla Robert E. Hormann René Lafont Josep Coll |
spellingShingle |
Laurence Dinan Pauline Bourne Pensri Whiting Ada Tsitsekli Ziyadilla Saatov Tarlochan S. Dhadialla Robert E. Hormann René Lafont Josep Coll Synthesis and biological activities of turkesterone 11?-acyl derivatives Journal of Insect Science steroid ecdysteroid 20-hydroxecdysone QSAR steroid hormone receptor |
author_facet |
Laurence Dinan Pauline Bourne Pensri Whiting Ada Tsitsekli Ziyadilla Saatov Tarlochan S. Dhadialla Robert E. Hormann René Lafont Josep Coll |
author_sort |
Laurence Dinan |
title |
Synthesis and biological activities of turkesterone 11?-acyl derivatives |
title_short |
Synthesis and biological activities of turkesterone 11?-acyl derivatives |
title_full |
Synthesis and biological activities of turkesterone 11?-acyl derivatives |
title_fullStr |
Synthesis and biological activities of turkesterone 11?-acyl derivatives |
title_full_unstemmed |
Synthesis and biological activities of turkesterone 11?-acyl derivatives |
title_sort |
synthesis and biological activities of turkesterone 11?-acyl derivatives |
publisher |
Oxford University Press |
series |
Journal of Insect Science |
issn |
1536-2442 |
publishDate |
2003-02-01 |
description |
Turkesterone is a phytoecdysteroid possessing an 11alpha-hydroxyl group. It is an analogue of the insect steroid hormone 20-hydroxyecdysone. Previous ecdysteroid QSAR and molecular modelling studies predicted that the cavity of the ligand-binding domain of the ecdysteroid receptor would possess space in the vicinity of C-11/C-12 of the ecdysteroid. We report the regioselective synthesis of a series of turkesterone 11alpha-acyl derivatives in order to explore this possibility. The structures of the analogues have been unambiguously determined by spectroscopic means (NMR and low-resolution mass spectrometry). Purity was verified by HPLC. Biological activities have been determined in Drosophila melanogaster BII cell-based bioassay for ecdysteroid agonists and in an in vitro radioligand-displacement assay using bacterially expressed D. melanogaster EcR/USP receptor proteins. The 11alpha-acyl derivatives do retain a significant amount of biological activity relative to the parent ecdysteroid. Further, although activity initially drops with the extension of the acyl chain length (C2 to C4), it then increases (C6 to C10), before decreasing again (C14 and C20). The implications of these findings for the interaction of ecdysteroids with the ecdysteroid receptor and potential applications in the generation of affinity-labelled and fluorescently-tagged ecdysteroids are discussed. |
topic |
steroid ecdysteroid 20-hydroxecdysone QSAR steroid hormone receptor |
url |
http://www.insectscience.org/3.6/ |
work_keys_str_mv |
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