Houseflies synergists

The edible parts of parsnips (Pastimea sativa L.), which have been consumed for centuries by humans without causing any obvious harm, were found to contain a chemical of insecticidal and strong synergistic nature (1). The insecticidal constituent, present at about 200 p.p.m., was isolated and identified as 5-allyl-l-methoxy-2, 3-methylenedioxybenzene or myristicin. Its toxicity to various insects [vinegar flies, houseflies, Mediterranean fruit flies, mosquito larvae, Mexican bean beetles, and pea aphids] was established and compared with pyrethrum and aldrin (Tables I and II). The knockdown effect, although definite, was not as great as that of pyrethrum. In tests... 

Jasmolin II in pure form was nearly equal to cinerin II in toxicity to houseflies but much less when synergized. The synergistic factor of the synergized compounds is pyrethrum extract 9.6 jasmolin II, 7.0 cinerin II, 12.0. 

Muscalure 20, the pheromone of the housefly has been prepared from oleic acid or erucic acid, similarly (Z)-l 1-heneicosene 21, the synergist of muscalure was obtained [189]. The intermediate 22 for the pheromone of the Cabbage looper was prepared using (Z)-methyl-4-octenedioate [166bJ, that was obtained by partial ozonolysis of (Z,Z)-l,5-cyclooctadiene. Similarly disparlure 23, the sex attractant of the gypsy moth, has been synthesized by two successive crossed-couplings with (Z)-4-octene dioate [191],... 

The sevenfold activity against houseflies credited to DFDT by the Germans actually represents the comparative activity of Gix, the active constituent of which is DFDT. It is possible that the other constituents of Gix acted as a synergist for the DFDT. Alessan-drini (2) reports the isolation from Gix of a compound melting at 99° to 100° C., which obviously is not DFDT. A crude sample of DFDT, a sample of recrystallized DFDT, and a sample of the impurities separated in the recrystallization of DFDT were found by Fay... 

At this time I was interested in the natural tolerance of houseflies to structural analogues of dieldrin and, with Harrison, I soon showed that whereas tolerance to cyclodienes was often related to oxidative detoxication and could be reduced or eliminated by benzodioxole synergists, dieldrin-resistance in houseflies did not respond to synergism and was apparently not a consequence of oxidative detoxication (33) Several laboratories (for their subsequent reviews see 34-36) confirmed the importance of oxidative biotransformations in insects and in 1964-5, at Slough, J. W Ray showed that microsomal preparations from houseflies and other insects contained cytochrome P450 (37) Thus, the links between insect and mammalian biochemical pharmacology were finally and firmly established. 

From an anticholinesterase/in vivo toxicity point of view, these molecules are perhaps the most interesting. They are as effective in some cases (2-F, I.q 2.1x10 M) as the best 5-methoxy compound (I5Q 1.6x10 8M), and yet their whole insect toxicity on houseflies is less. Again, without studies incorporating synergists into the toxicity evaluations, it is not possible to determine the reasons for the discrepancy between the n vitro and in... 

Sawicki. R.M. (1974). Genetics of resistance of a dimethoate-selected strain of houseflies iMusca domestics ..) to several insecticides and met by le ned ioxypheny synergists. J. Agric. Food Client. 22. 344-349,... 

Berova, M. and Barthel, W.F. (I957j. Chemical strueturc and activity of pyiethrin and allellirin synergists for cor tin l of the housefly. J. Agrk. Food Cttem. 5, 855-859. 

Table IV lists the insecticidal activity of cyclic sulfites In this case, the exo cyclic sulfites of 5,6-bis(hydroxymethyl)-7-isopropylidenebicyclo[2.2 l]hept-2-ene [20] was active whereas the corresponding endo Isomer [18] was inactive Monoepoxldation [21 and 22] and diepoxidation [23] of the exo cyclic sulfite resulted in a slight increase in activity Compound 15 was the most active among this series of compounds The LD q value of this compound was estimated to be about 1 pg/fly when topically applied to houseflies without any synergists (data not shown) The C-7 isopropylidene group proved to be unnecessary for high activity by comparison with compound 18. The activity decreased after epoxidation [16] or hydrogenation [17] of the endocyclic double bond The cyclodiene insecticide endosulfan was about 10 times as active as [15] ...

A priori there is good reason to believe that inhibitors of CYP enzymes may influence the synthesis or degradation of ecdysteroids and juvenile hormones, and thus interfere with the normal development of insects this is the case. Piperonyl butoxide, a well-known CYP enzyme inhibitor that is widely used as a synergist for pyrethrins, retards the development of houseflies and other insects by a few days. The mechanism is probably an interference with the metabolism of JH and not JH activity. 

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