Synthesis and SAR of cis‐1‐Benzoyl‐1,2,3,4‐tetrahydroquinoline Ligands for Control of Gene Expression in Ecdysone Responsive Systems.

Smith, Howard C.; Cavanaugh, Caitlin K.; Friz, Jennifer L.; Thompson, Christine; Saggers, Jessica A.; Michelotti, Enrique L.; Garcı́a, Javier; Tice, Colin M.

doi:10.1002/chin.200335116

Cited by 11 publications

(26 citation statements)

References 1 publication

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“…The results from these assays revealed that the THQ compound, RG-120768 is a good lead compound for mosquito control (Table 1). These results are in agreement with the finding of Smith et al who reported that some THQ analogs activate reporter genes through AaEcR in transactivation assays performed in mammalian cells (Smith et al, 2003).…”

Section: Discussionsupporting

confidence: 93%

“…1), by reaction of cis-6-fluoro-2-methyl-4-(4-fluorophenylamino)-1,2,3,4-tetrahydroquinoline (1) with a substituted benzoyl chloride (2) in the presence of base has been described previously (Kumar et al, 2004;Smith et al, 2003). RH-2485 and RG-102240 are synthetic stable ecdysteroid agonists synthesized at Rohm and Haas Company.…”

Section: Ligandsmentioning

confidence: 99%

“…The THQ compounds showed weak insecticidal activity against Heliothis virescens. Since then, several THQ compounds have been synthesized and tested for their ability to mediate the transactivation of a reporter gene through EcR from Aedes aegypti (AaEcR) (Smith et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Several classes of non-steroidal ecdysone agonists have since been developed Smith et al, 2003;Tice et al, 2003a,b). The THQ (1-aroyl-4-(arylamino)-1,2,3,4-tetrahydroquinoline) ligand class was identified by FMC Corporation using EcRs from Drosophila melanogaster, Heliothis virescens, and Plodia interpunctata in a cellbased assay (Dixson et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Biochemical mode of action and differential activity of new ecdysone agonists against mosquitoes and moths

Palli

Tice²,

Margam

et al. 2005

Arch Insect Biochem Physiol

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THQ (1-aroyl-4-(arylamino)-1,2,3,4-tetrahydroquinoline) compounds were identified by FMC Corporation in cell-based assays that used ecdysone receptors from Drosophila melanogaster, Heliothis virescens, or Plodia interpunctata. THQ compounds showed weak insecticidal activity against H. virescens and, therefore, were not developed further. Several ecdysone agonists based on THQ chemotype have been synthesized and tested for their activity against a number of EcRs in transactivation assays. The THQ compound, RG-120768, activated AaEcR (EcR from A. aegypti) but did not activate EcRs cloned from other insects. In transactivation assays, all six THQ ligands tested functioned through AaEcR but not through CfEcR (EcR from Choristoneura fumiferana). Three THQ compounds that showed higher activity in transactivation assays were tested in tobacco bud moth, H. virescens, and yellow fever mosquito, A. aegypti. These compounds showed higher activity in A. aegypti when compared to their activity in H. virescens. These data show that the THQ ligands are a new class of non-steroidal ecdysone agonists with preferential activity against mosquitoes.

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Section: Discussionsupporting

confidence: 93%

Section: Ligandsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Biochemical mode of action and differential activity of new ecdysone agonists against mosquitoes and moths

Palli

Tice²,

Margam

et al. 2005

Arch Insect Biochem Physiol

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“…DAHs are particularly useful for gene-switch systems incorporated into plants (e.g., Tavva et al, 2007), where ecdysteroids do not penetrate well enough. Two other classes of non-steroidal agonists are being assessed: a-amidoketones (Tice et al, 2003a,b) and tetrahydroquinolines (Smith et al, 2003;Palli et al, 2005a,b), of which the use of the latter appears limited as they are cytotoxic (Panguluri et al, 2007).…”

Section: Gene-switch Elicitorsmentioning

confidence: 99%

The Karlson Lecture. Phytoecdysteroids: What use are they?

Dinan

2009

Arch Insect Biochem Physiol

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Phytoecdysteroids are analogues of arthropod steroid hormones found in plants, where they deter predation by non-adapted predators. There is potential to exploit this to develop new strategies for pest control, either by using ecdysteroids as lead molecules for the design of novel pest control agents or by alteration of ecdysteroid levels/profiles in crop plants through plant breeding or genetic modification. However, it is other properties of phytoecdysteroids that have led to a rapid recent increase in scientific and commercial interest in these molecules. They are apparently non-toxic to mammals and a wide range of beneficial pharmacological (adaptogenic, anabolic, anti-diabetic, hepatoprotective, immunoprotective, wound-healing, and perhaps even anti-tumour) activities is claimed for them. In particular, this has led to a large (and unregulated) market for ecdysteroid-containing preparations for body-builders, sportsmen, and pets, among others. Ecdysteroids are also being considered as nutraceutical additives to food products. Further, ecdysteroids are good candidates as elicitors for gene-switch systems to be used in medical gene therapy and research applications. In this article, I review the applications of phytoecdysteroids and assess their future potential.

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New reporter gene assays for detecting natural and synthetic molting hormone agonists using yeasts expressing ecdysone receptors of various insects

et al. 2017

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Synthetic nonsteroidal ecdysone agonists, a class of insect growth regulators ( IGR s), target the ecdysone receptor (EcR), which forms a heterodimer with ultraspiracle ( USP ) to transactivate ecdysone response genes. These compounds have high binding affinities to the EcR– USP complexes of certain insects and their toxicity is selective for certain taxonomic orders. In the present study, we developed reporter gene assay ( RGA ) systems to detect molting hormone (ecdysone) activity by introducing EcR– USP cDNA and a bacterial lacZ reporter gene into yeast. EcR and USP were derived from the insect species of three different taxonomic orders: Drosophila melanogaster (Diptera), Chilo suppressalis (Lepidoptera), and Leptinotarsa decemlineata (Coleoptera). Transcriptional coactivator taiman (Tai) cDNA cloned from D. melanogaster was also used in this RGA system. This yeast RGA system responded to various EcR ligands in a dose‐dependent and ecdysteroid‐specific manner. Furthermore, the insect order‐selective ligand activities of synthetic nonsteroidal ecdysone agonists were linearly related to their binding activities, which were measured against in vitro translated EcR– USP complexes. Our newly established yeast RGA is useful for screening new molting hormone agonists that work selectively on target insects.

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Synthesis and SAR of cis‐1‐Benzoyl‐1,2,3,4‐tetrahydroquinoline Ligands for Control of Gene Expression in Ecdysone Responsive Systems.

Cited by 11 publications

References 1 publication

Biochemical mode of action and differential activity of new ecdysone agonists against mosquitoes and moths

Biochemical mode of action and differential activity of new ecdysone agonists against mosquitoes and moths

The Karlson Lecture. Phytoecdysteroids: What use are they?

New reporter gene assays for detecting natural and synthetic molting hormone agonists using yeasts expressing ecdysone receptors of various insects

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