Masayuki Hamada

Quantitative structure-activity studies of pyrethroids: 17. Physicochemical substituent effects of substituted benzyl esters of “Kadethric” acid on symptomatic and neurophysiological activities

Abstract The lethal and convulsive activities against American cockroaches and the knockdown activity against house flies of a set of meta -substituted benzyl esters of the acid component of kadethrin were measured under conditions in which metabolic factors were eliminated as much as possible. The neuroexcitatory and blocking activities in central nerve cords excised from the cockroaches were measured by an extracellular recording technique. Variations in each activity were analyzed quantitatively by use of physicochemical and structural parameters of the aromatic substituents and by regression analysis. The results indicated that variations in each activity other than neuroblocking activity could be analyzed by the hydrophobicity and steric dimensions of the substituents as well as factors arising from olefinic and ether bondings in particular positions of the substituents. The greater the hydrophobicity and the smaller the dimensions in terms of the length and the maximum width of the substituents, the higher were the activities. The neuroblocking activity decreased with the length of substituents when contributions from the above-mentioned structural factors were eliminated. Variations in the whole-body symptomatic activities were related to those in the neurophysiological activities in addition to the hydrophobic factors. The cockroach symptomatic activities increased with both the neuroexcitatory and blocking activities. The knockdown activity in house flies varied mostly with the neuroblocking activity.

Quantitative structure-activity studies of pyrethroids. 21. Substituted benzyl esters of "kadethric" acid and depolarization of the axonal membrane of crayfish.

Abstract The effects of a set of kadethrin analogs in which the alcohol moiety was replaced by various meta -substituted benzyl groups on the resting membrane potential in crayfish giant axons were measured with an intracellular recording technique. These compounds depolarized the membrane to various extents. Variations in the rate of depolarization, estimated from the time required to reach half the maximum depolarization, were related parabolically to the hydrophobicity of the compounds. Depolarization within 30 min after the start of treatment with each compound was mostly related to an increase in the axonal membrane permeability for sodium ions. With prolonged treatment, other factors, such as the loss of the ion selectivity of channels (perhaps caused by damage of the membrane structure), became progressively more important with time. Two kinds of depolarizing potency parameters, one mainly due to the change in permeability to sodium ions and the other including other factors, were defined and estimated from membrane potentials observed under different conditions. When the effect of the hydrophobicity of the compounds on the transport process was considered separately, such whole-body symptomatic activities as lethal and convulsive activities against American cockroaches and knockdown activity against house flies were correlated well to the depolarizing potency parameters. The higher depolarizing activity correlated well with higher whole-body activities.

Quantitative structure-activity studies of pyrethroids: 26. Rates of development of knockdown and depolarizing effects induced by “kadethric” acid esters and related compounds

Abstract The intrinsic knockdown activity of substituted benzyl esters of “kadethric” acid and related compounds on house flies was measured under synergistic conditions to inhibit metabolic activities. The rate constant of development of the knockdown symptom was estimated from the intrinsic knockdown activity and the activity at the earliest stage of intoxication by first-order kinetics with a two-compartment model. Variations in the rate constant were analyzed quantitatively with physicochemical molecular parameters and regression analysis. The analysis gave a parabolic relationship with hydrophobicity except for some compounds. The depolarization of the cockroach axonal membrane caused by the compounds was measured by an intracellular recording technique. The rate of depolarization was measured as the half-time in minutes required to attain half the maximum response after the start of treatment with each compound. Variations in the rate also were parabolically related to the hydrophobicity.

Quantitative structure-activity studies of pyrethroids: Depolarizing effect of pyrethroids on axonal membranes of American cockroaches

Abstract The depolarizing effect of a set of pyrethroids on the axonal membranes of American cockroaches was measured with an intracellular recording technique. Shortly after treatment with a compound, depolarization started because of an increase in the sodium permeability of axonal membranes. The relationships of depolarizing activity with nerve blocking activity in the central nerve cord and with insect killing activity were analyzed quantitatively with the least squares method. When the hydrophobicity of the compounds was taken into consideration, the neuroblocking activity was linearly related to the depolarizing activity. The higher the depolarizing activity and the greater the hydrophobicity, the higher was the neuroblocking activity. The lethal activity also was correlated with the depolarizing activity. These results suggest that the depolarization of the membrane is a key factor for pyrethroids to cause the conduction block of impulses, resulting in the symptom of intoxication in insects.

Isolation of Iridoid Glucosides from Paederia scandens and Assay of Biological Activities.

ヤイトバナより paederoside (Pa), paederosidic acid (Paa) ならびに scandoside (Sca) のイリドイド配糖体3化合物を単離した。これら化合物の生理活性を評価するために, ヤエムグラ種子より既に単離されている asperuloside (Asp) と deacetyl asperulosidic acid (Daa) ならびにDaaより誘導した deacetyl asperuloside (Da) を供試して比較検討した (Fig. 1)。その結果, ラクトン環をもつPaでは顕著な生長抑制を示すが, ラクトン環が開環しているPaaでは活性が低下し, Paaの脱アセチル体であるScaでは活性が著しく弱く, レタス幼苗に対しては, 伸長促進作用を示した。またこれらの結果は, 比較化合物として供試したAsp, DaaおよびDaによる活性とも類似の傾向を示し, ラクトン環をもつAspやDaで強い抑制作用を示すことより, イリドイド配糖体による植物生長抑制作用にラクトンが関与していることを確認した (Table 1, 2, 3)。

Neurophysiological effects of insecticidal pyrethroids and methoxychlor and of the anticalmodulin agent W-7

Abstract 1. W-7, an anticalmodulin agent, prolonged the falling phase of the action potential in crayfish ( Procambarus clarkii ) giant axons, as did meta -methylbenzyl pyrethrate, a pyrethroid insecticide, and the methoxychlor of a DDT analog. 2. The anticalmodulin agent suppressed both the inward and outward membrane currents in the axon, measured under voltage-clamp conditions. 3. The pyrethroid and methoxychlor insecticides induced a large inward tail-current upon step repolarization, but the anticalmodulin agent did not induce a current of a detectable size.