Inhibition of dipteran larval neuromuscular synaptic transmission by analogues of philanthotoxin-4.3.3: a structure-activity study.
1. The blocking action of delta-philanthotoxin (PhTX-4.3.3), a wasp toxin composed of a polyamine chain, an aromatic amino acid (tyrosyl) nucleus and an aliphatic (butanoic) acid was studied, together with 33 structural analogues, at the glutamatergic neuromuscular synapse in larvae of the house fly, Musca domestica. 2. Shortening of the polyamine or the aliphatic acid chain, or removing the aromatic nucleus caused a decrease in potency. 3. An increase in potency was obtained by elongating the molecule in any of several directions: elongation of the polyamine chain with amine containing groups, by iodination of the aromatic moiety and by aliphatic or aromatic elongation of the butanoic acid.
Plant Protection Division, CIBA-GEIGY Ltd, Basel, Switzerland.
J A
JA
Benson
F
F
Schürmann
L
L
Kaufmann
L
L
Gsell
T
T
Piek
D000818:Animals; D004175:Diptera / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000502:physiology; D018698:Glutamic Acid; D007814:Larva / Q000502:physiology; D009433:Neural Inhibition; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D011073:Polyamines; D013329:Structure-Activity Relationship; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D014862:Wasp Venoms / Q000633:toxicity*
D005971:Glutamates; D011073:Polyamines; D014862:Wasp Venoms; D018698:Glutamic Acid; C034092:delta-philanthotoxin