The polyhydroxylated derivatives of 6-keto,7-dehydrocholesterol (ecdysone, ecdysteroids, Ecd) are natural compounds widely distributed in plants. They exhibit strong anabolic, vitamin D-like, pharmacological effects in vertebrate animals and in the human body. In the larval stages of insects, injections of pure Ecd cause serious pathophysiological, "hyperecdysonic" syndromes associated with neuromuscular paralysis, premature cuticular apolysis and complete inhibition of ecdysis. Ecds do not penetrate insect cuticle. For this reason, all previous attempts to induce ecdysone responses by topical applications of Ecd failed. In this work, we tried to induce the topical effects of Ecd by preparation of more lipophilic complexes, with 2 or 4 molecules of 20-hydroxyecdysone (E20) attached to a relatively large nucleus of the porphyrin. The resulting porphyrin-E20 complexes (ecdysogens) have been subjected to standardised assays for ecdysone activity in the ligatured larvae ("dauerlarvae") of the greater waxmoth (Galleria mellonella). Similarly like the free E20 alone, porphyrin-E20 complexes had no effect when applied on the body surface or administered in the larval diet. When injected, however, they exhibited delayed effects, but the adverse ("hyperecdysonic") pathophysiological syndromes were reduced or abolished. It is concluded, therefore, that the replacement of pathophysiological, precocious or "hyperecdysonic" moults by the larval-pupal transformation, was due to successive metabolic liberation of the biologically active, free E20 from the porphyrin-E20 complex. The biological status of Ecd does not agree with their definition as the prothoracic gland (PG) hormone of insects, nor with the assumptions about a growth hormone of plants. A possibility that the most important status of Ecd may depend on the pharmacological properties of a sterolic D6 vitamin has been discussed.

• Klíčová slova
• 20-hydroxyecdysone (E20), Ecdysone, Ecdysone bioassays, Ecdysteroids (Ecds), Galleria mellonella, Hyperecdysonic syndromes, Neuromuscular paralysis by Ecd,
• MeSH
• aplikace lokální MeSH
• aplikace orální MeSH
• biologická proměna účinky léků   MeSH
• ekdysteron aplikace a dávkování   chemie   farmakologie   fyziologie   MeSH
• kukla účinky léků   MeSH
• larva účinky léků   MeSH
• Lepidoptera účinky léků   fyziologie   MeSH
• porfyriny chemie   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ekdysteron MeSH
• porfyriny MeSH

The biological activities of selected specific ecdysteroids obtained by photochemical or chemical transformation are compared in the B(II) bioassay, in which the potency reflects the affinity of binding to the ligand-binding site of the Drosophila melanogaster ecdysteroid receptor. The compounds tested represent 14-deoxy, 14-dehydroxy, 14-hydroperoxy and 14-epi derivatives of 20-hydroxyecdysone and were selected on the basis of their close structural relationship to elucidate the contribution of the 14-hydroxy group and the stereochemical configuration at C-14 to ecdysteroid agonist activity. The structure-activity relationship shows that a 14-hydroxy group is not required for activity. However, the alpha-configuration of -H, -OH or -OOH at C-14, which determines the C/D rings trans-annelation, is very significant for activity; it is as important for activity as the well studied A/B rings cis-annelation. Compounds containing a double bond involving C-14 showed low activity with the exception of the specific, and so far unique, ecdysteroid dimer 7,7'-bis-[14-deoxy-8(14)-ene-20-hydroxyecdysone], which was obtained as the main product of the photochemical transformation of 20-hydroxyecdysone. The relatively high biological activity of this dimeric compound is discussed.

• MeSH
• biotest MeSH
• buněčné linie MeSH
• dimerizace MeSH
• Drosophila melanogaster MeSH
• ekdysteron analogy a deriváty   chemie   MeSH
• molekulární struktura MeSH
• steroidní receptory metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ecdysteroid receptor MeSH Prohlížeč
• ekdysteron MeSH
• steroidní receptory MeSH

Structural modification of 20-hydroxyecdysone (20E) based on photochemical transformation yielded dimeric ecdysteroid 7alphaH,7'alphaH-bis-[(20R,22R)-2beta,3beta,20,22,25-pentahydroxy-5beta-cholest-8(14)-en-6-one-7-yl] as a main product. Its structure was determined by detailed NMR analysis. Furthermore, two new monomeric analogues: 14-epi-20-hydroxyecdysone and 14-deoxy-14,18-cyclo-20-hydroxyecdysone were identified in addition to the earlier described 14-deoxy and 14-hydroperoxy derivatives of 20E. Formation of the specific and so far unique ecdysteroid dimer has not been observed in earlier photo-transformation studies. The transformed dimeric analogue of 20-hydroxyecdysone retained the high agonistic activity on the ecdysone receptor in the B(II)-bioassay compared with the original 20E.

• MeSH
• dimerizace MeSH
• Drosophila melanogaster MeSH
• ekdysteroidy analogy a deriváty   MeSH
• ekdysteron chemická syntéza   chemie   MeSH
• fotochemie metody   MeSH
• magnetická rezonanční spektroskopie MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• spektrofotometrie infračervená MeSH
• steroidní receptory agonisté   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ecdysone receptor MeSH Prohlížeč
• ekdysteroidy MeSH
• ekdysteron MeSH
• steroidní receptory MeSH