Preparation and biological assessment of hydroxycinnamic acid amides of polyamines.
Many plants contain hydroxycinnamic acid conjugates of polyamines that are remarkably similar in general structure to the acylated polyamines found in spider and wasp toxins. In an effort to determine whether these compounds might play a role in the chemical defense of plants against arthropod pests we synthesized a variety of analogues of the coumaric (4-hydroxycinnamic) acid conjugates of di-, tri-, and tetraamines using common protection and acylation strategies. N(1)- and N(8)-coumaroyl spermidine were tested in feeding trials with insect larvae including the European corn borer (Ostrinia nubilalis), the tobacco budworm (Heliothis verescens) and the oblique banded leaf roller (Choristoneura rosaceana). Antifeedant assays with the rice weevil Sitophilus oryzae were also performed. Neither the naturally occurring coumaric acid conjugates of polyamines nor their analogues showed notable toxicity towards insects, despite precautions to maintain these easily oxidized materials in the wet diet. However, more direct bioassays of these compounds on glutamate dependent neuroreceptors including the deep abdominal extensor muscles of crayfish, or mammalian NMDA, delta2, and AMPA receptors, clearly showed that these compounds were inhibitory. N(1)-Coumaoryl spermine, a dodecyl and a cyclohexyl analogue were especially active at NMDA NR1/NR2B receptors. The latter had an IC(50) of 300 microM in the crayfish. N(1)-Coumaroyl spermine had an IC(50) in the crayfish preparation of 70-300 microM and against the mammalian NR1/NR2B receptor of 38 nM. Structure-activity variations show similar trends of length and hydrophobicity as has been seen previously with analogues of spider toxins. We conclude from this work that while the coumaric acid polyamine conjugates are active when directly applied to neuroreceptors, they show no overt toxicity when ingested by insect larvae.
Department of Chemistry, Brock University, St.Catharines, L2S3A1, Ontario, Canada.
Solomon
S
Fixon-Owoo
Frédéric
F
Levasseur
Keith
K
Williams
Thomas N
TN
Sabado
Mike
M
Lowe
Markus
M
Klose
A
A
Joffre Mercier
Paul
P
Fields
Jeffrey
J
Atkinson
D000215:Acylation; D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D003400:Astacoidea / Q000187:drug effects / Q000502:physiology; D003373:Coumaric Acids / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D007313:Insecta / Q000187:drug effects; D007814:Larva / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011073:Polyamines / Q000737:chemistry* / Q000494:pharmacology*; D011422:Propionates; D017470:Receptors, Glutamate / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013095:Spermidine / Q000031:analogs & derivatives / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014981:Xenopus
D000577:Amides; D003373:Coumaric Acids; D011073:Polyamines; D011422:Propionates; D017470:Receptors, Glutamate; D011994:Recombinant Proteins; D018698:Glutamic Acid; C495469:p-coumaric acid; D013095:Spermidine