Practical uses for ecdysteroids in mammals including humans: and update

Lafont, René; Dinan, Laurence

doi:10.1093/jis/3.1.7

Cited by 127 publications

(131 citation statements)

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“…[4] As a consequence of their ability to mimic the actions of arthropod moulting hormones while being non-toxic to vertebrates, phytoecdysteroids are interesting lead compounds for the development of environmentally friendly invertebrate pest control agents. [5] Furthermore, steroidal and non-steroidal ligands for natural and mutated EcRs have been used successfully in EcR-based inducible gene expression systems for the modulation of the expression of a gene of interest within a host cell [6] and animal models. [7] Geneswitch technology finds applications in several fields of the life sciences, including functional genomics, drug discovery and gene therapy.…”

Section: Introductionmentioning

confidence: 99%

Absolute Configuration and Docking Study of Canescensterone, a Potent Phytoecdysteroid, with Non‐Lepidopteran Ecdysteroid Receptor Selectivity

et al. 2010

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Section: Introductionmentioning

confidence: 99%

Absolute Configuration and Docking Study of Canescensterone, a Potent Phytoecdysteroid, with Non‐Lepidopteran Ecdysteroid Receptor Selectivity

et al. 2010

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“…The non-hormonal biological activity of ecdysteroids towards mammals is intensively studied [4][5][6]. It has been reported that non-polar ecdysteroids possess chemo-sensitizing activity towards various cancer cell lines [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…Some ecdysteroids act as hormone antagonists, disturbing insect molting process [2]; however, these compounds cannot efficiently affect the population of insects, which has acquired defense mechanisms against exogenous ecdysteroids during evolution. In view of this fact, a synthesis of novel ecdysteroid analogues would provide compounds for efficient regulation of vital processes in insects [3].The non-hormonal biological activity of ecdysteroids towards mammals is intensively studied [4][5][6]. It has been reported that non-polar ecdysteroids possess chemo-sensitizing activity towards various cancer cell lines [7][8][9][10].…”

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Oxo-analogues of 20-hydroxyecdysone in the synthesis of novel fluorinated ecdysteroid derivatives

et al. 2018

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Novel side chain ω-fluorinated ecdysteroid analogues were obtained starting from ω-functionalized ecdysteroids. Thus, the reaction of diacetonides of 26, derivatives with diethylaminosulfur trifluoride (DASТ) involves replacement of the terminal hydroxyl group and dehydration at the 14-position to give 25RS-fluoro-and 24-fluoro-14-anhydro analogues of ecdysteroids. IntroductionEcdysteroids are known as insect hormones which control molting, metamorphosis, and reproduction [1]. Some ecdysteroids act as hormone antagonists, disturbing insect molting process [2]; however, these compounds cannot efficiently affect the population of insects, which has acquired defense mechanisms against exogenous ecdysteroids during evolution. In view of this fact, a synthesis of novel ecdysteroid analogues would provide compounds for efficient regulation of vital processes in insects [3].The non-hormonal biological activity of ecdysteroids towards mammals is intensively studied [4][5][6]. It has been reported that non-polar ecdysteroids possess chemo-sensitizing activity towards various cancer cell lines [7][8][9][10]. The fluorination of steroids, juvenile hormones, and pheromones can influence the biological activity of these compounds [11]. The interest in fluorinated analogues of natural compounds is caused by features of the fluorine atom, which significantly affects the biological activity and the metabolic stability of a molecule due to high electronegativity, and small size and to low polarizability of the C-F bond. Thus, the introduction of fluorine atom in natural products is the attractive strategy to obtain new leads for drug discovery [12]. The most common synthetic route to fluorinated derivatives is fluorination with various nucleophilic reagents [13]. Among them, diethylaminosulfur trifluoride (DAST) is widely used in deoxyfluorination of oxygen-containing organic compounds; moreover, this reagent is effective for geminal fluorination of acid-sensitive substrates such as aldehydes and ketones [14].The aim of the present study was to involve new side chain analogues of 20-hydroxyecdysone in the DAST-fluorination and to extend the scope of the reaction to the synthesis of biologically active fluorinated analogues of ecdysteroids. In this regard, we began our research from the study of DAST fluorination of the side chain-modified oxoecdysteroids 1 and 2, which were obtained by the ozonolysis of ∆ 24,25 -and ∆ 25,26 -derivatives of 20-hydroxyecdysone [16]. It should be noted that 20-hydroxyecdysone is a polyhydroxylated molecule with three secondary and three tertiary hydroxyl groups and it reacts with the DAST reagent to give a complex reaction mixture. DAST fluorination of ecdysteroids 1 and 2 Results and Discussionhaving an acid-sensitive γ-hydroxy-α,β-enone moiety gave only 14-anhydro derivatives 3 and 4. Moreover, it was found that the oxo groups of ecdysteroid side chain are inert to the DAST-mediated geminal difluorination. That is why terminal alcohols 5 and 6 were chosen as alternative precursors for t...

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“…It was found that ecdysteroids are nontoxic for warm-blooded animals. Versatile physiological effect of ecdysteroids on humans and animals was revealed: they were found to control mineral, carbohydrate, lipid, and protein exchange, normalize sugar and cholesterol concentration in blood, stimulate hemopoietic activity, and exert immunomodulatory effect [3]. The diversity of physiological action of ecdysteroids is determined to some extent by their antioxidant properties, for many diseases are related to oxidative stress [4].…”

mentioning

confidence: 99%

“…On the other hand, the substituents on C 2 and C 3 in the 1,3-dioxolane ring of the 2,3-acetal moiety differ only slightly, and the C 2″′ chiral acetal carbon atom gives only one peak in the 13 C NMR spectrum. Protons at the C 2″′ and C 2″″ acetal carbon atoms in V resonated in the 1 H NMR spectrum as broadened singlets (w 1/2 = 13 Hz) at δ 5.18 (20,22) and 5.24 ppm (2,3).…”

mentioning

confidence: 99%

(6-Benzyloxy-2,5,7,8-tetramethylchroman-2-yl)acetaldehyde conjugates with 20-hydroxyecdysone, stachysterone B, and their 20,22-acetonides

et al. 2010

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Conjugates consisting of ecdysteroid and α-tocopherol analog fragments were synthesized for the first time from 20-hydroxyecdysone and (6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl)acetaldehyde.Ecdysteroids (insect ecdysis, metamorphosis, and diapause hormones) are present not only in insect organisms, but also (in considerably higher concentrations) in plants from which these unique polyhydroxylated sterols were isolated. The properties and some chemical transformations of ecdysteroids were studied [1,2]. It was found that ecdysteroids are nontoxic for warm-blooded animals. Versatile physiological effect of ecdysteroids on humans and animals was revealed: they were found to control mineral, carbohydrate, lipid, and protein exchange, normalize sugar and cholesterol concentration in blood, stimulate hemopoietic activity, and exert immunomodulatory effect [3]. The diversity of physiological action of ecdysteroids is determined to some extent by their antioxidant properties, for many diseases are related to oxidative stress [4].We believed that a promising way of enhancing pharmacological effect of ecdysteroids may be conjugation with natural phenolic antioxidants such as α-tocopherol and its analogs. For this purpose, we examined reactions of 20-hydroxyecdysone (I) and its 2,3-and 20,22-acetonides II and III with (6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl)acetaldehyde (IV). The reaction of ecdysteroid I with 2 equiv of aldehyde IV, catalyzed by phosphomolybdic acid (PMA), gave 62% of the corresponding bis-adduct V (Scheme 1). This reaction occurred at a higher rate in the presence of p-toluenesulfonic acid as catalyst, but the yield of bis-acetal V did not change. Bis-adduct V was also formed in the reaction of 20-hydroxyecdysone 2,3-acetonide (II) with an equimolar amount of aldehyde IV in the presence of TsOH or PMA, but the yield was lower (35%). Under analogous conditions, from 20,22-acetonide III we obtained 60% of 2,3-adduct VI. Presumably, the formation of bis-adduct V from 2,3-acetonide II is favored due to known lability of compound II in acid medium [1].Apart from 20-hydroxyecdysone conjugates V and VI, from the reaction mixtures we isolated the corresponding 14,15-anhydro derivatives VII and VIII in 26 and 20% yield, respectively. Compounds VII and VIII can be regarded as analogous stachysterone B conjugates. 20-Hydroxyecdysone conjugates V and VI were subjected to debenzylation by hydrogenation over Pd/C in ethanol solution. As a result, the corresponding hydroxy derivatives IX and X were smoothly formed. The MALDI-TOF mass spectrum of bis-adduct IX contained [M + H] + ion peak. In the 1 H and 13 C NMR spectra of compounds V-X we observed signals from all protons iand carbon nuclei in the ecdysteroid and chroman fragments, in keeping with the assumed structure of their molecules.Monoadduct VI displayed in the 13 C NMR spectrum (in the region typical of acetal carbon atoms) signals from quaternary (δ C 106.97 ppm) and tertiary (δ C 101.97 ppm) carbon atoms in the 20,22-O-isopropylidene (cf. [5]) and eth...

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Practical uses for ecdysteroids in mammals including humans: and update

Cited by 127 publications

References 176 publications

Absolute Configuration and Docking Study of Canescensterone, a Potent Phytoecdysteroid, with Non‐Lepidopteran Ecdysteroid Receptor Selectivity

Absolute Configuration and Docking Study of Canescensterone, a Potent Phytoecdysteroid, with Non‐Lepidopteran Ecdysteroid Receptor Selectivity

Oxo-analogues of 20-hydroxyecdysone in the synthesis of novel fluorinated ecdysteroid derivatives

(6-Benzyloxy-2,5,7,8-tetramethylchroman-2-yl)acetaldehyde conjugates with 20-hydroxyecdysone, stachysterone B, and their 20,22-acetonides

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