Ecdysteroid antagonists

The ecdysteroid antagonists identified to date are all of rather low potency This may be a consequence of them all being plant natural products, which the plant is able to produce in high concentrations at low cost to itself [231],... 

Table 7 Relative potencies of known ecdysteroid antagonists in the Drosophila melanogaster Bn bioassay. EC50 values were determined in the presence of 5 x 10 8M 20-hydroxyecdysone. Only compounds for which it was possible to determine distinct EC50 values are included.

The plant-insect chemical interactions concerning the stilbenoids have just been reviewed [509] (-i-)-Ampelopsin B (806) and ct-viniferin (635) antagonized the action of 20-hydroxyecdysone [510] cw-miyabenol A (735), kobophenol B and cw-miyabenol C (663) showed competitive binding to ecdysteroid receptors [337] resveratrol (1) and oligomers (suffruticosols A-C, 589-591) also exhibited ecdysteroid antagonistic activity [297]. 

Ecdysteroids are the steroid hormones of insects, where they regulate moulding and metamorphosis. As ecdysteroids are essential to the normal development of insects, it was presumed that some plant secondary metabolites might have the ecdysteroid antagonistic activity and be capable of affecting insect development. Such compounds would be useful... 

Dinan L. reported that three resveratrol trimers, suffruticosols A (100), B (101), C (102), and one monomer cis resveratrol from Paeonia suffruticosa are active as ecdysteroids (antagonists (EDso) 10-50 pM vs. 5xlO 8pM of 20-hydroxyecdyson), but inactive as agonists in the Drosophila melanogaster BII cell bioassay for ecdysteroids agonists/ antagonists [75]. 

Many secondary metabolites found in plants deter phytophagous invertebrates, sometimes even modifying insect growth and development if included in the diet [8]. Natural products can often act as insecticides via different pathways, as is the case with the analogues of insect juvenile hormones produced by plants. Thus, some derivatives of these analogues are used as commercial insecticides while others act as ecdysteroid antagonists [8]. 

Further studies have indicated that 1 and its oligomers may be capable of inhibiting insect predation by serving as ecdysteroid antagonists [80], In vitro studies have shown that m-resveratrol (98) and suffruticosols A-C (52-54) may interact with insect ecdysteroid receptors in an antagonistic fashion, thereby preventing proper growth and development of the insect to occur. 

Sarker SD, Whiting P, Dinan L (1999) Identification and ecdysteroid antagonist activity of three resveratrol trimers (suffruticosols A, B and C) from Paeonia suffruticosa. Tetrahedron 55 513-524... 

The study of Savchenko et al. (2000) on solanaceous species described also ecdysteroid antagonist activity of solanaceous extracts. However, only weak activity was associated with a few of such extracts. Major withanolides were inactive, but they may be activated by metabolism after ingestion by invertebrate predators. 

---