Michael Elliott's billion dollar crystals and other discoveries in insecticide chemistry

The crowning achievement for Michael Elliott came in 1973 when his most outstanding candidate insecticide from 25 years of research crystallized from hexane solution. The stereochemically pure crystalline compound was the most potent synthetic insecticide ever made until that time, and it was highly selective for insects compared with mammals. It was given the name deltamethrin. Sequential stereospecific crystallization to isolate the most potent epimer and base‐catalyzed racemization of the remaining less active isomer could be used to produce deltamethrin efficiently on a large scale; it became the billion dollar crystals. Elliott's discoveries at Rothamsted in England with Norman Janes and David Pulman of resmethrin, permethrin, cypermethrin and ultimately deltamethrin provided crop protection and malaria control for millions of people. Michael also laid the background for lipophilic amide, dithiane and other insecticides and nerve probes that are not involved in pyrethroid cross‐resistance. Some aspects of these investigations were best conducted at Berkeley, where Michael studied pyrethrins in 1969, synthetic pyrethroids in 1974 and alternative insecticides in 1986–1988. This review considers Michael's seminal discoveries in insecticide chemistry, with emphasis on his Berkeley years. Copyright © 2010 Society of Chemical Industry     

蚊耐氯菊酯C6/36细胞构建及耐药相关基因PR-XP1的表达分析

建立蚊耐氯菊酯C6/36细胞,并探讨PR-XP1基因与蚊C6/36细胞对氯菊酯的耐药性之间关系.采用逐步诱导法筛选蚊耐氯菊酯C6/36细胞,观察耐药细胞形态变化、生长状态,测定生长曲线和半数致死剂量;利用荧光实时定量PCR鉴定PR-XP1基因在敏感细胞与耐药细胞中的表达差异.获得耐400μg/mL氯菊酯的C6/36细胞;实时定量PCR检测发现抗药基因PR-XP1在蚊耐氯菊酯C6/36细胞中表达量明显上升.表明构建蚊耐氯菊酯C6/36细胞是研究蚊虫氯菊酯耐药性的有效方法,初步证明PR-XP1基因表达升高可能与蚊虫对氯菊酯的耐药性具有一定的相关性.     

Acaricide resistance and synergism between permethrin and amitraz against susceptible and resistant strains of Boophilus microplus (Acari: Ixodidae)

The control of the southern cattle tick, Boophilus microplus (Canestrini), in Mexico and many other countries relies on chemical acaricides. Boophilus microplus has developed resistance to all major classes of acaricides in recent years. To gain a better understanding of the resistance and to develop resistance management strategies that benefit both Mexican ranchers and USDA's cattle fever tick eradication program (CFTEP), the authors used larval bioassay techniques to determine levels of resistance to permethrin and amitraz and then evaluated synergism between these two acaricides in one susceptible laboratory tick strain and four resistant strains originating from Mexico and Brazil. To examine mechanisms of resistance to permethrin in these strains, the frequency of a mutated sodium channel gene was determined using a PCR assay. The tick strains from Mexico and Brazil demonstrated 49.4- to over 672.2-fold resistance to permethrin, and up to 94.5-fold resistance to amitraz. While the San Roman strain from Mexico was the most permethrin-resistant strain, the Santa Luiza strain from Brazil was the most amitraz-resistant strain. A significant correlation was found between the permethrin resistance ratio and the allelic frequency of the sodium channel mutation. Significant synergism between permethrin and amitraz was found when one acaricide was tested in the presence of another. Synergism ratios ranged from 1.5 to 54.9 when amitraz was tested as a synergist for permethrin. Similar synergism ratios were obtained when permethrin was tested as a synergist for amitraz. Permethrin caused virtually no mortality in the San Roman strain, even at the highest concentration (3294 microg cm(-2)). Adding amitraz (11.0 microg cm(-2)) to permethrin led to a dramatic increase in larval mortality, even at very low concentrations of permethrin.     

Molecular analysis of pyrethroid resistance conferred by target insensitivity and increased metabolic detoxification in Plutella xylostella

BACKGROUND: The pyrethroid resistance of the diamondback moth Plutella xylostella (L.) is conferred by increased gene expression of cytochrome P450 to detoxify the insecticide and/or through gene mutation of the sodium channel, which makes the individual insensitive to pyrethroids. However, no information is available about the correlation between the increased metabolic detoxification and the target insensitivity in pyrethroid resistance. RESULTS: Frequencies of pyrethroid‐resistant alleles (L1014F, T929I and M918I) and two resistance‐related mutations (A1101T and P1879S) at the sodium channel and expression levels of the cytochrome P450 gene CYP6BG1 were examined individually using laboratory and field strains of P. xylostella. Real‐time quantitative PCR analysis using the laboratory strains revealed that levels of larval expression of the resistant strain, homozygous for the pyrethroid‐resistant alleles other than the M918I, are significantly higher than those of the susceptible strain. In the field strains, the expression levels in insects having the same resistant alleles as those of the resistant strains varied greatly among individuals. The expression levels were not significantly higher than those in the heterozygotes. CONCLUSION: Significant correlation between the target insensitivity and the increased metabolic detoxification in pyrethroid resistance of P. xylostella was observed in the laboratory but not in the field. Copyright © 2010 Society of Chemical Industry     

Molecular cloning and gene expression of two cytochrome P450s from permethrin-resistant Culex quinquefasciatus larvae

As part of a continuing study of factors influencing the development of pesticide resistance in insects, two new cytochrome P450s of the CYP6 family have been identified.     

氯菊酯的毛细管气相色谱分析

介绍了用 SE-52毛细管柱气相色谱、FID 检测器,以癸二酸二辛酯为内标的氯菊酯定量分析方法。本方法成功地分离了氯菊酯的顺、反异构体。测得方法变异系数为0.45%,氯菊酯顺、反异构体的比例为43.6:56.4,平均添加回收率为100.10%,线性相关系数为0.9988。     

Synergism by Propynyl Aryl Ethers in Permethrin-Resistant Tobacco Budworm Larvae,Heliothis virescens

Synergists were used to diagnose possible mechanisms of permethrin resistance in permethrin-selected strains of the tobacco budworm, Heliothis virescens (F.). In addition to permethrin, these strains of the tobacco budworm were resistant to α-cyano-pyrethroid insecticides, organophosphorus insecticides and DDT. The monooxygenase-inhibiting prop-2-ynyl aryl ethers were the only effective synergists of permethrin among 16 candidates tested. The most effective synergist was 1,2,4-trichloro-3-(2-propynyloxy)benzene. Piperonyl butoxide, a common monooxygenase-inhibiting synergist in other species and tobacco budworm strains, was inactive. These results suggested the presence and contribution of an unusual monooxygenase in the enzymatic detoxication of permethrin. DDT cross-resistance, which was not synergized, and broad pyrethroid cross-resistance supported previous evidence for target site insensitivity as a second pyrethroid-resistance mechanism in these strains. The actions of S,S,S-tributyl phosphorotrithioate (TBPT) and triphenyl phosphate (TPP) suggested that hydrolytic detoxication, important in methyl parathion-resistance tobacco budworm strains, had little or no role in conferring pyrethroid resistance in these strains.     

Laboratory evaluation of fipronil,a phenylpyrazole insecticide,against adult Anopheles (Diptera: Culicidae) and investigation of its possible cross‐resistance with dieldrin in Anopheles stephensi

Adult mosquitoes from two strains of Anopheles gambiae and from three strains of Anopheles stephensi were exposed to 0.25% fipronil‐treated papers in WHO test kits or to 500 mg fipronil m⁻² impregnated mosquito netting in bioassay spheres. For comparison, tests were also carried out with the pyrethroid permethrin, using the same methods and doses, and on papers treated with 0.4 and 4% of the cyclodiene insecticide dieldrin. Compared with the same doses of permethrin, fipronil showed less and delayed activity. Two of the An stephensi strains were resistant to fipronil and dieldrin. To investigate whether this was due to a resistance mechanism in the An stephensi strains acting against both insecticides, the most fipronil‐ and dieldrin‐tolerant strain was further selected in two separate lines with one of the insecticides, followed by tests with the insecticide that the line had not been selected with. This indicated a concomitant rise of resistance to dieldrin in the fipronil‐selected line and vice versa. Repeated back‐crossing of the two lines with a susceptible strain and re‐selection with either dieldrin or fipronil gave evidence for the involvement of a single resistance mechanism to both insecticides. Permethrin resistance in both lines declined with selection for dieldrin or fipronil and confirms the absence of cross‐resistance between fipronil and pyrethroids. © 2001 Society of Chemical Industry