Synthesis and herbicidal activity of 3-substituted toxoflavin analogs

We investigated the synthesis and herbicidal activity of 23 toxoflavin analogs, 1a–w, in which aromatic rings (R) were introduced into the C-3 position. In paddy field conditions, 1k (R=2-CF₃–C₆H₄) and 1w (R=2-thienyl) showed excellent herbicidal activity. Under upland field conditions, we found that toxoflavin analogs 1a (R=C₆H₅), 1n (R=2-CH₃O–C₆H₄), and 1p (R=4-CH₃O–C₆H₄) exhibited wide herbicidal spectrum against Echinochloa crus-galli (L) var. crus-galli (ECHCG), Chenopodium album, and Amaranthus viridis (AMAVI). The analog with the 2-fluoro group on benzene ring 1b also showed high herbicidal activity against both ECHCG and AMAVI.     

Synthesis and characterization of a group of dihydropyrimido-benzimidazole photosystem II herbicides

A group of 28 dihydropyrimido-benzimidazole analogs and derivatives was tested for herbicidal activities. The 1:1 mixture of 7-fluoro- and 8-fluorodihydropyrimido-benzimidazole had the greatest biological activity. Activity is increased by methylation of nitrogen 2. None of the active compounds was inhibitory to nonphotosynthetic tissue-culture cells in vitro. The I₅₀ of inhibition of growth of green duckweed plants and that of in vitro photosynthesis activity matched the I₅₀ of inhibition of photosystem II activity. Fluorescence analyses of photosystem II activity indicated inhibition at the same step as did many triazine, phenylurea, pyridazinone, and uracil herbicides. As the compounds showed insufficient activity on recently evolved triazine-resistant weed biotypes, their further development was terminated, despite their novel chemistry.     

Environmental degradation of the insect growth regulator methoprene: V. Metabolism by houseflies and mosquitoes

The metabolism of methoprene (I, isopropyl (2E,4E)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate, trademark Altosid) was investigated in larval mosquitoes and houseflies. The most abundant primary metabolite in third- and fourth-instar Aedes and fourth-instar Culex larvae was the hydroxy ester while the hydroxy acid predominated in third-instar Musca larvae. Biological isomerization of the double bond at C-2 in I (i.e., conversion of (E) to (Z)) was an effective mode of insect detoxication, but these dipterans apparently cannot isomerize the (2Z) isomer of I to methoprene. In general, piperonyl butoxide and triorthocresyl phosphate slightly increased the morphogenetic activity of I in these insects.     

米尔贝霉素类似物的合成及杀螨杀蚜活性

为寻找高活性的米尔贝霉素衍生物,以伊维菌素为原料,经脱糖、羟基保护、氧化、还原胺化、脱保护等将其转变为13-氨基米尔贝霉素类似物,通过三组分反应设计合成了一系列米尔贝霉素磺酰脒类化合物(7a~7i),并初步测定了其对朱砂叶螨Tetranychus cinnabarinus和豆蚜Aphis craccivora的室内活性。结果表明:各衍生物对朱砂叶螨和豆蚜均有较好的触杀活性,其中7f、7h和7i对朱砂叶螨24 h的LC50值分别为1.04×10–2、9.60×10–4和1.44×10–2 mg/L;7i对豆蚜24 h的LC50值为7.81 mg/L。米尔贝霉素13位氨基上磺酰化的结构修饰有助于提高米尔贝霉素类化合物的杀螨、杀蚜活性。     

Chemical structure-activity relationships of the inhibition of sterol biosynthesis by N-substituted morpholines in higher plants

Tridemorph and fenpropimorph as well as several related N-alkyl morpholines have been tested in vitro on the cycloeucalenol-obtusifoliol isomerase, a microsomal enzyme involved in higher plant sterol biosynthesis. The results showed that N-substituted morpholines inhibit powerfully the enzyme (I₅₀ = 0.4 μM for fenpropimorph). The following important molecular parameters of the inhibition could be determined: (i) the inhibitory capacity was probably related to the presence of a positive charge on the nitrogen atom, (ii) the length of the alkyl group was critical, with a maximum activity for n = 13 carbons in the case of a linear hydrocarbon chain, (iii) the presence of bulky substituents at the proximity of the nitrogen atom led to a strong decrease of the inhibitory power, (iv) in the fenpropimorph series where a chiral center is present at C-2 of the alkyl chain, a remarkable enantiomeric selectivity of the inhibition was observed, (v) the N-oxide derivative of fenpropimorph was shown to be as active as the parent compound. The N-alkyl morpholines have been also assayed on suspension cultures of bramble cells and led to a strong accumulation of 9β, 19-cyclopropyl- and Δ⁸-sterols. This result confirmed that the cycloeucalenol-obtusifoliol isomerase was a major target of the N-substituted morpholines and suggested that the Δ⁸ → Δ⁷-sterol isomerase was also a target for these chemicals. The molecular parameters implied in the in vivo accumulation of 9β, 19-cyclopropyl sterols were very similar to those resulting from the in vitro study. The chemical structure-inhibitory activity relationship of N-alkyl morpholines was discussed with respect to their fungicidal activity which has been described in a previous study [E. H. Pommer, Pestic. Sci. 15, 285 (1984)]. The comparison revealed that the better the inhibitory capacity on the cycloeucalenol-obtusifoliol isomerase was, the higher was the fungicidal activity in vivo.     

Insecticidal 3-benzamido-N-phenylbenzamides specifically bind with high affinity to a novel allosteric site in housefly GABA receptors

γ-Aminobutyric acid (GABA) receptors (GABARs) are an important target for existing insecticides such as fiproles. These insecticides act as noncompetitive antagonists (channel blockers) for insect GABARs by binding to a site within the intrinsic channel of the GABAR. Recently, a novel class of insecticides, 3-benzamido-N-phenylbenzamides (BPBs), was shown to inhibit GABARs by binding to a site distinct from the site for fiproles. We examined the binding site of BPBs in the adult housefly by means of radioligand-binding and electrophysiological experiments. 3-Benzamido-N-(2,6-dimethyl-4-perfluoroisopropylphenyl)-2-fluorobenzamide (BPB 1) (the N-demethyl BPB) was a partial, but potent, inhibitor of [³H]4′-ethynyl-4-n-propylbicycloorthobenzoate (GABA channel blocker) binding to housefly head membranes, whereas the 3-(N-methyl)benzamido congener (the N-methyl BPB) had low or little activity. A total of 15 BPB analogs were tested for their abilities to inhibit [³H]BPB 1 binding to the head membranes. The N-demethyl analogs, known to be highly effective insecticides, potently inhibited the [³H]BPB 1 binding, but the N-methyl analogs did not even though they, too, are considered highly effective. [³H]BPB 1 equally bound to the head membranes from wild-type and dieldrin-resistant (rdl mutant) houseflies. GABA allosterically inhibited [³H]BPB 1 binding. By contrast, channel blocker-type antagonists enhanced [³H]BPB 1 binding to housefly head membranes by increasing the affinity of BPB 1. Antiparasitic macrolides, such as ivermectin B_1a, were potent inhibitors of [³H]BPB 1 binding. BPB 1 inhibited GABA-induced currents in housefly GABARs expressed in Xenopus oocytes, whereas it failed to inhibit l-glutamate-induced currents in inhibitory l-glutamate receptors. Overall, these findings indicate that BPBs act at a novel allosteric site that is different from the site for channel blocker-type antagonists and that is probably overlapped with the site for macrolides in insect GABARs.     

Thiophene carboxamide fungicides: Structure-activity relationships with the succinate dehydrogenase complex from wild-type and carboxin-resistant mutant strains of Aspergillus nidulans

Carboxin (5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxanilide) and the thiophene compound 3-methylthiophene-2-carboxanilide (I), inhibit succinate oxidation (succinate-ubiquinone reductase; complex II) in mitochondria from a wild-type strain and three mutant, carboxin-resistant strains of Aspergillus nidulans. Studies by White et al. [Pestic. Biochem. Physiol. 9, 165–182 (1978)] showed that certain oxathiin carboxamide structures were selectively active against particular mutated succinate dehydrogenase complexes (SDCs) of A. nidulans, significantly lowering the level of resistance. Although no oxathiin carboxamides were found to be negatively correlated to carboxin with respect to their effect on SDCs from wild-type and mutant strains of A. nidulans, several could distinguish between moderately and highly carboxin-resistant SDCs and, as shown in the present study, between the two non-allelic highly carboxin-resistant mutants cbx B-28 and cbx C-34. Variation in the molecular structure of thiophene carboxamides can also affect the phenotypic expression of mutations to carboxin resistance in the SDC of A. nidulans, with certain structures being capable of differentiating between moderately and highly carboxin-resistant mutated SDCs. With a moderately carboxin-resistant mutant, cbx A-17, a wide structural variety of thiophene carboxamides, e.g., the 2′-methyl, 2′-benzoyl, 3′-phenoxy, 4′-nbutyl and the N-nhexyl derivatives of (I), did exhibit negative activity correlation to the parent anilide (I). However, with the possible exception of the 4′-nbutyl and 4′-noctyloxy analogs of (I), thiophene carboxamides showed no negative activity correlation to carboxin or (I) for the highly carboxin-resistant mutants cbx B-28 and cbx C-34. As with carboxin-resistant mutants of Ustilago maydis [Pestic. Biochem. Physiol. 14, 26–40 (1980)], molecular selectivity for mutated carboxin-resistant SDCs of A. nidulans can be markedly influenced by substitution of an oxathiin with a thiophene heterocyclic ring. None of the thiophene carboxamides were considerably toxic to mycelial growth of the wild-type and carboxin-resistant strains of A. nidulans with permeability rather than affinity for the SDC appearing to be the limiting factor. For certain derivatives such as the 5-amino analog of (I), SDC activity and cell growth were inhibited similarly. Several thiophene carboxamides [2′-phenyl, 4′-phenoxy, and N-ndecyl analogs of (I)] showed specificity for the highly carboxin-resistant mutants cbx B-28 and cbx C-34. Thiophene carboxamide structures have been identified which inhibit spore germination of non-Basidiomycete plant pathogens, particularly Phytophthora infestans and Verticillium dahliae. In vivo experiments with late blight (P. infestans) on tomato plants have shown that a few thiophene carboxamides, e.g., the 3′-nbutyl analog of (I) give satisfactory protectant activity.     

Albumin and cytochrome P450 binding characteristics of juvenile hormone and its analogs

Binding data were gathered for the cecropia juvenile hormone (methyl(E, E cis)-10,11-epoxy-7-ethyl-3,11-dimethyl-2,6-tridecadienoate) and two of its analogs {isopropyl(2E, 4E)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate; (E)-4-[(6,7-epoxy-3,7-dimethyl-2-nonenyl)-oxyl]-1,2-(methylenedioxy)benzene} with bovine serum albumin and rat hepatic microsomal cytochrome P₄₅₀. The proteins were found to bind the juvenile hormone and juvenile hormone analogs with affinity constants ranging from 10⁵ to 10⁶M^?1. Thermodynamic calculations suggest that the binding of all three compounds is electrostatic in nature and that the size of the ether and ester substituents can greatly influence the binding to proteins. The juvenile hormone and its analogs all formed spectrally apparent Type I complexes with oxidized cytochrome P₄₅₀; one of the juvenile hormone analogs formed a spectrally observable product adduct with reduced cytochrome P₄₅₀. The product complex may contribute many of the hormonal effects observed for this compound.     

Synthesis and fungicidal activities of positional isomers of the N-thienylcarboxamide

To investigate the effects of bioisosteric replacement of the phenyl group with the thienyl group, N-phenylcarboxamide and three regioisomers of N-(substituted-thienyl)carboxamide were synthesized. The inhibitory activity on the succinate dehydrogenase prepared from the gray mold Botrytis cinerea as well as the fungicidal activity against B. cinerea were evaluated. Two isomers, N-(2-substituted-3-thienyl)carboxamide and N-(4-substituted-3-thienyl)carboxamide exhibited the same level of activity as the phenyl derivative, whereas N-(3-substituted-2-thienyl)carboxamide exhibited lower activity than the phenyl derivative, suggesting that the 2-substituted-3-thienyl and 4-substituted-3-thienyl groups functioned as bioisosteres of the phenyl group in N-phenylcarboxamide, but the other did not.     

The pyrethrins and related compounds. Part XXVIII: Alkenyl- and alkynyl-substituted benzyl esters

Over 100 benzyl esters of pyrethroidal acids were synthesised and tested for insecticidal activity to establish detailed structure–activity relationships in compounds with side-chains similar to those in the natural pyrethrins. Alkenyl, and corresponding alkynyl, side-chains were effective, both at the 3- and 4-positions, as were side-chains with extended substitution in either E or Z forms. A cyano group at the α-position increases activity if the side-chain is at C-3, but lowers it drastically if the substituent is at C-4. Similarly, methyl groups at C-2 and/or C-6 may increase activity whether the unsaturated side-chain is at C-3 or C-4, but only in the absence of an α-cyano group.     

Isolation of a phytotoxic isocoumarin from Diaporthe eres‐infected Hedera helix (English ivy) and synthesis of its phytotoxic analogs

BACKGROUND

The fungus Diaporthe eres was isolated from a fungal pathogen‐infected leaf of Hedera helix (English ivy) exhibiting necrosis. It is hypothesized that the causative fungus produces phytotoxins as evidenced by necrotic lesions on the leaves.

RESULTS

The fungus was isolated and grown in Czapek Dox broth culture medium and potato dextrose broth culture medium and identified as Diaporthe eres. The ethyl acetate extracts of the culture broths were phytotoxic to lettuce (Lactuca sativa) and bentgrass (Agrostis stolonifera). 3,4‐Dihydro‐8‐hydroxy‐3,5‐dimethylisocoumarin ( 1 ) and tyrosol ( 2 ) were isolated and identified as the phytotoxic constituents. Six analogs of 3,4‐dihydro‐isocoumarin were synthesized and shown to be phytotoxic. The synthesized 3,4‐dihydro‐8‐hydroxy‐3,7‐dimethylisocoumarin and 3,4‐dihydro‐8‐hydroxy‐3,3,7‐trimethylisocoumarin were two‐ to three‐fold more phytotoxic than the naturally occurring 1 in a Lemna paucicostata growth bioassay.

CONCLUSION

Synthesis and herbicidal activities of the several new analogs of 1 are reported for the first time. These promising molecules should be used as templates for synthesis and testing of more analogs. © 2017 Society of Chemical Industry     

Dimethoxypyrimidines as novel herbicides. Part 4. Quantitative structure–activity relationships of dimethoxypyrimidinyl(thio)salicylic acids

The activity of a number of O-(4,6-dimethoxypyrimidin-2-yl)salicylic acids and their thio analogs inhibiting acetolactate synthase (ALS) preparation was measured. The effects of substituents on the salicylic-benzene ring on the inhibitory activity were analyzed quantitatively with physicochemical substituent parameters. For 6-substituted (thio)salicylic acids, the activity was shown to vary parabolically with the ‘intramolecular’ steric parameter ( E_s ). In addition, the higher steric dimension of substituents in terms of the STERIMOL width or length parameter lowered the activity. The field-inductive electron-withdrawing property of the 6-substituents in terms of the Swain–Lupton–Hansch F was favorable for the activity of salicylic acid series. In 5-substituted salicylic acids, the activity was increased by electron-donating substituents with smaller size. The relationships between ALS inhibitory and herbicidal activities were also analyzed with some weed species. Both pre- and post-emergence activities against barnyard grass, Echinochloa crus-galli, were linearly related to the ALS inhibitory activity after allowing for the hydrophobic factor that may contribute to the transport processes. Those against two broad-leaved weed species, Polygonum convolvulus and Abutilon theophrasti were linearly related to the in-vitro activity with no significant participation of the hydrophobic factor. © 1998 SCI     

Studies on the inhibition of methanogenesis and dechlorination by (4-hydroxyphenyl) chloromethanesulfonate

The purpose of this study was to demonstrate the inhibitory effect of chemicals on methane emissions in paddy soil. We found that (4-hydroxyphenyl) chloromethanesulfonate (C-1) has a methanogenic inhibition activity, and we studied its inhibition mechanism using laboratory tests. The study found that C-1 treatment of flooded soil did not significantly affect the bacterial community but rather the archaeal community; particularly, Methanosarcina spp. C-1 strongly inhibited the aceticlastic methanogenesis route. It was suggested that the inhibitory target of C-1 was different from the well-known methanogenic inhibitor 2-bromoethanesulfonate, which targets methyl-coenzyme M reductase of methanogen. In addition, C-1 had a secondary effect of inhibiting the dechlorination of chlorophenols. Although field trials are required as the next development step, C-1 can be used to reduce methane emissions from paddy fields, one of the largest sources in the agricultural sector.     

Antifungal mode of action of triforine

Rapidly growing mycelia of Aspergillus fumigatus treated with 10 μg/ml triforine (N,N′-bis-(1-formamido-2,2,2-trichloroethyl)-piperazine) showed little or no inhibition in dry weight increase prior to 2 h. By 2.5–3 h, triforine inhibited dry weight increase by 85%. The effects of triforine on protein, DNA, and RNA syntheses corresponded to the effect on dry weight increase both in time of onset and magnitude. Neither glucose nor acetate oxidation were inhibited by triforine.Ergosterol synthesis was almost completely inhibited by triforine even in the first hour after treatment. Inhibition of ergosterol synthesis was accompanied by an accumulation of the ergosterol precursors 24-methylenedihydrolanosterol, obtusifoliol, and 14α-methyl-Δ^{8, 24 (28)}-ergostadienol. Mycelia treated with 5 μg/ml of triarimol (α-(2,4-dichlorophenyl)-α-phenyl-5-pyrimidinemethanol) also accumulated the same sterols as well as a fourth sterol believed to be Δ^{5, 7}-ergostadienol.Identification of 4,4-dimethyl-Δ^{8, 24 (28)}-ergostadienol in untreated mycelia indicates that the C-14 methyl group is the first methyl group removed in the biosynthesis of ergosterol by A. fumigatus. The lack of detectable quantities of 4,4-dimethyl-Δ^{8, 24 (28)}-ergostadienol in triforine or triarimol-treated mycelia and the accumulation of C-14 methylated sterols in treated mycelia suggests that both fungicides inhibit sterol C-14 demethylation. The accumulation of Δ^{5, 7}-ergostadienol in triarimol-treated mycelia further implies that triarimol also inhibits the introduction of the sterol C-22(23) double bond.Two strains of Cladosporium cucumerinum tolerant to triforine and triarimol were also tolerant to the fungicide S-1358 (N-3-pyridyl-S-n-butyl-S′-p-t-butylbenzyl imidodithiocarbonate).     

Toxicity of novel aromatic and aliphatic organic acid and ester analogs of trypsin modulating oostatic factor to larvae of the northern house mosquito, Culex pipiens complex, and the tobacco hornworm, Manduca sexta

Eight non-peptidic chemical analogs of trypsin modulating oostatic factor (TMOF, NH₂-YDPAP₆), an insect hormone inhibiting trypsin biosynthesis in mosquitoes, were synthesized based on the structure of the native peptide. The median lethal concentration (LC₅₀) for the chemical analogs, TMOF and FDPAP (a peptidic analog of TMOF) was estimated for larvae of the northern house mosquito, the Culex pipiens complex, using a static 5-day bioassay. Four of these compounds demonstrated the same larvicidal activity as TMOF, while three of these compounds were 1.2-2.5-fold more active than TMOF. The compounds introduced by injection were toxic to fourth instars of the tobacco hornworm, Manduca sexta, except for TMOF, FDPAP, and PPHEN. Injection of TMOF and FDPAP into fourth stadium and TMOF into second stadium M. sexta had no effect on trypsin activity, growth, or mortality. Apparently the mosquito hormone is inactive in the tobacco hornworm at the developmental stages examined. Three TMOF analogs (CHEA, PHEA, and PHA) demonstrating the highest activity by injection in M. sexta were also found to be toxic by injection in fourth instars of the tobacco budworm, Heliothis virescens, and the cotton bollworm, Helicoverpa zea, as well as adult male German cockroaches, Blattela germanica. A two-choice feeding bioassay with H. virescens indicated that at least one of the TMOF analogs, PHEA, has anti-feeding properties.     

Isolation of a novel Carica papaya α-amylase inhibitor with deleterious activity toward Callosobruchus maculatus

Cowpea (Vigna unguiculata) is a subsistence crop for small and poor farmers from Latin America and Africa. This culture is commonly damaged by cowpea weevil (Callosobruchus maculatus), which burrow into stored seeds to fed on. Due to impact of larval predation, several plant defense studies have been developed, indicating that α-amylase inhibitors are able to impede and/or reduce bruchids digestive process. In this report, a novel α-amylase inhibitor from papaya seeds (Carica papaya) with activity against cowpea weevil enzymes was purified and biochemical characterized. Peeled seeds were macerated and extracted with a 0.6 M NaCl and 0.1% HCl solution. Crude extract was precipitated with ammonium sulphate (100%). After dialyses, this rich fraction was applied onto a CM-Cellulose column and retained peak was submitted to an analytic reversed-phase column HPLC (Vydac C-18TP) yielding several peaks. Only one fraction, with molecular mass of 4562 Da, showed significant inhibitory activity against C. maculatus α-amylases. Otherwise, no inhibitory activities against mammalian α-amylases were observed. Bioassays using artificial seeds containing C. papaya α-amylase inhibitor rich fraction (0.5% and 1.0%) were also conduced showing that α-amylase inhibitors were able to increase larval mortality (50%) and also decrease insect fecundity and adult longevity. These results showed the presence of an α-amylase inhibitor from C. papaya seeds with high specificity to insect enzymes, indicating that this inhibitor probably could be used, through genetic engineering, in the construction of transgenic plants with enhanced resistance toward cowpea weevil.     

The breakdown of the triazine herbicide cyanazine in soils and maize

Radioisotope techniques have been used to study the breakdown products that are formed from the herbicide cyanazine ( BLADEX )^a, 2-chloro-4-(1-cyano-1-methylethyl-amino)-6-ethylamino-1,3,5-triazine, in soils and in maize grown in the soils under indoor conditions. In soils of different types cyanazine broke down mainly by conversion of the nitrile group to amide ( II ) and then to an acid ( III ) followed by hydrolysis of the ring chlorine to hydroxyl ( IV ). Dealkylation reactions occurred to only a limited extent in soils. In maize plants grown in treated soils the hydrolysis products, the amide ( II ) and the hydroxy acid ( IV ) were detected as well as appreciable quantities of products ( VI ) and ( VIII ) formed from these by loss of the N-ethyl group. In plants the hydroxy acids ( IV ) and ( VIII ) were present in the free form and there was also evidence for conjugates which were not identified but could be converted to these hydroxy acids, ( IV ) and ( VIII ), on treatment with acids. In these indoor studies the major residues appear to be the hydroxy acid ( IV ) in soils and ( IV ) and its dealkylated analogue ( VIII ) in plants grown in treated soils. These compounds are not herbicides and are of a low order of toxicity to mammals.     

Non-steroidal inhibitors of Drosophila melanogaster steroidogenic glutathione S-transferase Noppera-bo

Insect growth regulators (IGRs) can be developed by elucidating the molecular mechanisms of insect-specific biological events. Because insect molting, and metamorphosis are controlled by ecdysteroids, their biosynthetic pathways can serve as targets for IGR development. The glutathione S-transferase Noppera-bo (Nobo), which is conserved in dipteran and lepidopteran species, plays an essential role in ecdysteroid biosynthesis. Our previous study using 17β-estradiol as a molecular probe revealed that Asp113 of Drosophila melanogaster Nobo (DmNobo) is essential for its biological function. However, to develop IGRs with a greater Nobo inhibitory activity than 17β-estradiol, further structural information is warranted. Here, we report five novel non-steroidal DmNobo inhibitors. Analysis of crystal structures of complexes revealed that DmNobo binds these inhibitors in an Asp113-independent manner. Among amino acid residues at the substrate-recognition site, conformation of conserved Phe39 was dynamically altered upon inhibitor binding. Therefore, these inhibitors can serve as seed compounds for IGR development.     

2-苄硫基烟酰胺类衍生物的合成及生物活性

以2-苄硫基烟酸为原料,设计并合成了26个2-苄硫基烟酰胺类化合物,其化学结构经核磁共振氢谱和元素分析确证。初步的生物活性测定结果表明,该类化合物具有一定的杀虫及除草活性。其中 C-9、C-10、C-11 在50 mg/L时对淡色库蚊Culex pipiens pallens的致死率达到100％; C-3、C-6、C-15 在100 mg/L对稗草Echinochloa crusgalli Link、马唐Digitaria sanguinalis、苋菜Ambrosia tricolor Linn的白化度大于80％。     

Isoxaben analogs inhibit chitin synthesis in the cultured integument of the rice stem borer Chilo suppressalis

Benzoylphenylureas (BPUs) were discovered as novel type insecticides about a half century ago; many analogs have been launched as insecticides and acaricides. BPUs are known to inhibit chitin synthesis in insects and other arthropods, but they have no effect against microorganisms such as fungi. We designed new chitin synthesis inhibitors based on the hypothesis that biomolecules that play important roles in cellulose and chitin biosynthesis are similar. In the full automatic modeling system (FAMS), the cellulose synthase was selected as a template three-dimensional structure. Thus, we focused on the structure of cellulose synthase inhibitor, isoxaben, to develop new chemistry. The 1,1-diethylethyl [-C(CH₃)(CH₂CH₃)₂] group of isoxaben was changed to a 4-substituted phenyl group bearing Cl, Et, or Ph. These compounds significantly inhibited chitin synthesis in the cultured integument of the rice stem borer Chilo suppressalis. The activity of the 4-ethylphenyl analog was enhanced 30-fold by adding piperonyl butoxide to the culture medium.