STUDIES ON THE MECHANISM OF INSECTICIDAL ACTION OF ORGANO-PHOSPHORUS COMPOUNDS WITH PARTICULAR REFERENCE TO THEIR ANTIESTERASE ACTIVITY

The preparation of an extract of the mealworm larvae, Tenebrio molitor L. which hydrolyses ethyl butyrate and o -nitrophenyl acetate, but not acetylcholine, is described. The inhibition of this esterase by TEPP-containing materials and parathion was determined.
An enzyme that hydrolysed o -nitrophenyl acetate and was inhibited by a TEPP-containing material was demonstrated in the five other insect species used.
The relative toxicities as contact insecticides to adult Tribolium castaneum Hbst. of ten samples of TEPP-containing materials were compared with their relative activities as esterase inhibitors. There was not an exact quantitative correlation between TEPP content estimated chemically, insecticidal activity and anti-esterase activity; but the correlation was sufficient to suggest interdependence of these factors.
Eggs of Diataraxia oleracea L. and Ephestia kühniella Zell, were shown to contain an enzyme that hydrolysed o -nitrophenyl acetate and was inhibited by the TEPP-containing materials. This enzyme was present in eggs less than 24 hr. old, i.e. before there was any visible signs of development. The TEPP was shown to be toxic to these eggs and in high concentrations kills at an early stage of development before differentiation of the nervous system. This, in conjunction with the other evidence, suggests that esterases other than the choline-esterase of the nervous system are important when considering the toxic action of these compounds.
Comparison of the anti-esterase activity and toxicity of parathion and TEPP-containing materials as insecticides showed that although the TEPP materials were the more potent enzyme inhibitors, parathion was the more potent contact insecticide to five species of insects. This appears to be due to the relative instability of TEPP. The study of the rates of action of the two poisons applied at different concentrations supports this view.     

THE INSECTICIDAL ACTIVITY OF SOME ORGANOPHOSPHORUS COMPOUNDS AGAINST THE MIGRATORY LOCUST (LOCUSTA MIGRATORIA MIGRATORIOIDES REICHE & FAIRM.)

Although the insecticidal effectiveness of a compound is dependent on many factors, such as Solubilities and detoxification, there appear to be distinct relationships between chemical structure and insecticidal activity. The insecticidal activity of paraoxon was significantly greater to the adult males of Locusta migratoria migratorioides than that of all other nitrophenyl-phosphorus compounds tested. This may be attributed to the direct action of the compound, involving no change from inactive to active form in vivo , and also to a better translocation of the compound from the point of application to the site of action. The toxicity of injected paraoxon was of the same order as that topically applied. Parathion, its isomers, and ethyl p-nitrophenyl phenyl phosphonothionate (EPN) were approximately equivalent, whereas malathion, although relatively low in toxicity, with an ED₅₀, of 29 μg./insect, was still a reasonably effective insecticide. Methyl, ethyl and iso- propyl esters were effective in that order of toxicity. Substitution of other alkoxy or aryloxy groups resulted in loss of activity.     

THE INSECTICIDAL ACTIVITY OF SUBSTANCES RELATED TO THE PYRETHRINS

The toxicity as contact insecticides of the esters of (±)-3-methyl-2-allyl-cycfopent-3-en-4-ol-i-one with the natural (+ )-trans and with synthetic (±) -cis-trans-chrysaii- themum monocarboxylic acids has been compared with that of the natural pyrethrins. The comparison was carried out on five species of test-insects.
It was found that the figure for both the absolute and the relative toxicities of these compounds varied with the species used as test-subject.
The factors involved in this variation are discussed. The extremes of variation of relative toxicity for the compounds with the natural acid were from about one-eighth as toxic as the pyrethrum standard when the aphid Macrosiphum solanifolii was used as test subject to nearly four times as toxic as the standard with the larvae of the moth Plutella maculipennis. The fully synthetic material varied from about one-sixteenth as toxic as the standard to Macrosiphum solanifolii to nearly twice as toxic to the larvae of Plutella maculipennis. The compound with the natural acid was approximately twice as toxic as the fully synthetic material to three of the insect species, but the fully synthetic material was considerably more than half as toxic as the partially synthetic to the fourth test-species. It is pointed out that while it is widely recognized that large differences in relative toxicity may occur when the effect of chemicals of widely different structure and mechanism of action are compared on a number of different test-species, the fact that these differences may also occur with related chemicals with, presumably, a similar mechanism of action, has not been clearly stated.
Even when the differences in relative toxicity are taken into account, the two synthetic pyrethrin-like esters still show high insecticidal activity.
It seems reasonable to suppose from the results that economic commercial synthesis of pyrethrin-like insecticides is not impossible.     

INSECTICIDAL COMPOUNDS FROM THE FRUITS OF PHELUlDENDRON CHINENSE AGAINST HOUSEFLY

Abstract Three N-isobutylamides were isolated from the fruits of Phellodendron chinense . (2E, 4E)-N-isobutyl tetradecadienamide and (2E, 4E1-N-isobutyl pentadecadienamide were responsible for the in-secticidal activity against Musca domestica . However, (2E, 4E, 82)-N-isobutyl tetradecatrienamide was not active.     

THE TOXICITY OF CERTAIN SYNTHETIC ORGANIC COMPOUNDS TO THE FRUIT-TREE RED-SPIDER MITE

The acaricidal activity of ninety synthetic organic compounds has been investigated in the laboratory. Considerable differences were found between the winter eggs, the summer eggs and the adult female stages of the fruit-tree red-spider mite (Meta-tetranychus ulmi (Koch)) in their susceptibility to many of the compounds but two substances, namely azoxybenzene and n-dodecyl thiocyanate, were appreciably toxic to all three stages. Of the compounds showing promise against summer eggs and mites, bis-( p -chlorophenyl) methyl carbinol and 4-chloroazobenzene were the best, being highly toxic to both summer stages. Of the remainder, diphenylsulphone, 4-chlorodiphenylsulphone, azobenzene and hydrazobenzene were highly ovicidal, while C₁₂-C₁₃ alkyl thiocyanates and sec .-dodecyl thiocyanate gave high kills of the adult female mite.
Relationships between molecular structure and acaricidal activity have been sought. In a series of compounds characterized by the presence of two benzene nuclei connected by certain bridging groups, it has been found that activity to the summer stages of the mite can be influenced by alterations to the bridging group and by substitution in the benzene nuclei. Maximum activity appears to be associated with chlorine substitution in the para position in one nucleus and also with compounds of this type having unsubstituted nuclei.     

THE SYSTEMIC INSECTICIDAL ACTION OF CERTAIN COMPOUNDS OF FLUORINE AND OF PHOSPHORUS ON PHAEDON COCHLEARIAE FAB.

Four compounds— bis dimethylaminophosphonous anhydride (schradan), bis (dimethylamino)fluorophosphine oxide ( dimefox ), diethyl paranitrophenyl phosphate ( paraoxon ) and sodium fluoroacetate ( acetate )—have been tested against the mustard beetle, Phaedon cochleariae Fab. When the four compounds are compared by a direct contact technique in which insects can also imbibe some of the test solutions, or the insects are caged with foliage which has been dipped and then dried, the order of toxicity to adults and larvae was found to be Paraoxon > acetate ≏ dimefox > schradan.
The paraoxon is very much more toxic than the other compounds. In all cases the adults are more resistant than the larvae.
When the insecticides are applied systemically the order of toxicity changes to Paraoxon > dimefox > acetate ≏ schradan because the acetate causes the plants to wilt and less of it is absorbed. Both paraoxon and dimefox give complete kills of adult Phaedon which is the most resistant stage, at practical concentrations.
When the insecticides were applied to the outer leaves and translocated to the inner untreated leaves an effect was observed with the dimefox and paraoxon after numerous application, but with a single application very inconsistent results were obtained.
It is concluded that schradan and the acetate are ineffective systemically against Phaedon. The dimefox and paraoxon are very effective, but because of their high mammalian toxicity they would require very careful handling in practice.     

海藻中的细胞毒活性及抗菌成分

本文综述了近20年来海藻中的细胞毒活性及抗菌成分的研究概况。     

中药抗癌有效成份有机锗化合物的合成及其抗癌活性初探

本文报道了中药抗癌有效成份羰乙基锗倍半氧化物的类似物的合成及其抗癌活性的初步筛选结果。按所设计的 [(Ge CH (?) COy)_2O_3·mH_2O] 和[(Ge CH (?) COy)_2S_3] 两种类型,共合成了16个化合物,其中12个为新化合物,利用层析——酶抑制法对这16个化合物进行活性筛选的结果表明,其中8个化合物具有明显的抗癌活性。这一研究结果尚未见文献报道。     

THE SYSTEMIC INSECTICIDAL ACTION OF SODIUM FLUOROACETATE AND OF THREE PHOSPHORUS COMPOUNDS ON THE EGGS AND LARVAE OF PIERIS BRASSICAE L.

Four compounds, bis dimethylaminophosphonous anhydride ( anhydride ), bis (dimethylamino)fluorophosphine oxide ( oxide ), diethyl paranitrophenyl phosphate ( E 600) and sodium fluoroacetate ( acetate ), previously shown to have systemic insecticidal activity against aphids, have now been tested against the eggs and larvae of Pieris brassicae L.
The anhydride proved to have very little toxic action on Pieris , but the other three compounds showed both contact toxicity and systemic insecticidal action when taken up by the roots of cabbage plants from solution and from soil. The acetate, but more especially the E600, also showed systemic action following application to the leaves.
In all cases the order of decreasing toxicity was E600 > acetate > oxide > anhydride. E600 is the only compound which is outstandingly toxic to Pieris eggs and larvae. It has the added interest that when watered on to the roots of cabbage plants it kills larvae in egg batches on the leaves. Death takes place at the stage when the larvae are biting through the shells. The oxide and acetate proved to be surprisingly innocuous.
Unless it is felt to be too poisonous E600 is worthy of consideration as an insecticide against Pieris eggs and larvae, since it is highly effective as a contact insecticide and also has some systemic action.     

新农药克幼脲对小菜蛾和菜青虫的生物活性及防治效果试验

室内测定苯甲酰基苯脲类化舍物克幼脲对菜青虫、小菜蛾的致死中浓度分别为9．89ppm和28．44ppm。试验表明,该药剂药效迟缓,但持效期长,可显降低小菜蛾低龄幼虫的有效转化宰。克幼脲与其他化学农药具有良好的相溶性,混剂速灭脲1号,4号的速效性,持效期均优于单剂。     

INSECTICIDAL ACTIVITY AND CHEMICAL CONSTITUTION: ANALOGUES AND ISOSTERES OF DDT

A number of isosteres of DDT and related compounds have been synthesized and examined for insecticidal activity using the grain-weevil, locust and cotton stainer. A marked loss of activity follows replacement of the chlorine atoms of DDT by methyl and hydroxyl groups. In the nitroalkane series, the optimum structure for maximum toxicity was present in i:i-di-/>-chlorophenyl-2-nitropropane. The significance of these results has been reviewed in the light of current theories of DDT structure and activity. Many of the compounds expected to be toxic were found not to be so, and this inactivity can be attributed either to the initial hypotheses being invalid or to the operation of biological factors preventing concentration of the compound at the site of action.     

INCREASE OF DNA POLYMERASE ACTIVITY FIRMLY BOUND TO NUCLEI DURING THE DNA SYNTHETIC PHASE OF THE CELL CYCLE

DNA polymerase activities were measured on nuclear and supernatant fractions obtained from hamster fibroblast cells (the Don-C clone) grown in tissue culture and mitotically synchronized by selective removal of cells arrested in metaphase following a brief exposure to colcemid. A reproducible fraction (5–10%) of the polymerase activity was found to remain bound in the nuclear pellet after repeated cycles of freezing and thawing. The specific activity of this firmly-bound nuclear DNA polymerase was found to increase during S-phase in proportion to DNA synthesis. The bulk of this activity, after extraction in 1 m salt, exhibited an S value of 8·7 on neutral high salt sucrose gradients and was 24 times more active with poly dA. dT₁₀ as template than with heat denatured DNA. The rest of the cellular DNA polymerase activity showed no significant variation correlated with the cell cycle. This activity also had an S value from 8 to 9 but it was only 2·8 times more active with the homopolymer template than with heat denatured DNA. DNA polymerase activity similar to the firmly-bound activity was found in extracts prepared from metaphase chromosomes.     

SOME FACTORS INFLUENCING THE SENSITIVITY OF BODY TEMPERATURE TO ACTIVITY IN NEONATES

In adult humans, core temperature is influenced by activity; the sensitivity of core temperature to such effects shows a phase dependence and is also influenced by the environment and whether the individual is asleep or awake. We have investigated if similar effects are evident in neonates, in whom thermoregulation and the circadian rhythm of core temperature are not fully developed. Eleven full-term, healthy babies were studied singly (light 07:00–19:00) at 2 days of age and again 4 weeks after birth; between these times, they were tended routinely on a communal ward. On study days, 10-minute recordings were made of rectal and skin (abdominal) temperature, heart rate (HR), and behavioral state. Sensitivities of the temperatures to activity (“arousal”) were assessed throughout the 24h by measuring the gradient of (temperature/HR). Sensitivities measured at 01:00, 05:00, 09:00, 13:00,17:00, and 21:00 were used as dependent variables in stepwise regression and linear regression analyses, with “subjects” “light versus dark”, “behavioral state”, and “difference between time of measurement and the acrophase of the endogenous component of the temperature rhythm” (ignoring sign) as possible predictors. (Acrophases of the temperature rhythms had been estimated from 24h data purified using the behavioral state record.) Light versus dark acted as a significant predictor of the sensitivity of rectal temperature to arousal on day 2 and week 4, the sensitivity increasing in the light, and there was limited evidence for behavioral state acting as a predictor on day 2. Neither factor was a significant predictor when the sensitivity of the babies' skin temperatures to arousal was investigated. There was also some evidence that the difference between the time of measurement and the temperature acrophase acted as a predictor of sensitivity to arousal in both rectal (day 2) and skin (week 4) temperature, with larger differences decreasing the sensitivity. These results indicate that there are masking effects on body temperature due to arousal in neonates, the size of which depends on both internal and external factors. However, this sensitivity of temperature to arousal shows differences from the sensitivity of temperature to physical activity in both adult humans and adult mice. One possible explanation of this result is that temperature regulation and the circadian system are not fully developed in humans at this age. (Chronobiology International, 17(5), 679–692, 2000)