Chemical Models of Cytochrome P450 Catalyzed Insecticide Metabolism. Application to the Oxidative Metabolism of Carbamate Insecticides

Keserü, György M.; Balogh, György Tibor; Czudor, Irén; Karancsi, Tamás; Fehér, and András; Bertók, Béla

doi:10.1021/jf980347+

Cited by 20 publications

(11 citation statements)

References 26 publications

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“…Despite the good results obtained with the use of synthetic metalloporphyrins in drug oxidation, few studies have been devoted to the application of these models in pesticide transformation. Keseru ¨and co-workers are one of the few groups working in this field, and they have shown that Fe(TFPP)Cl can mimic the action of insect P450 in the chemical transformation of insecticides belonging to the carbamate class of compounds (7).…”

Section: Introductionmentioning

confidence: 99%

Metalloporphyrins as Biomimetic Models for Cytochrome P-450 in the Oxidation of Atrazine

Gotardo

Moraes

Assis

2006

J. Agric. Food Chem.

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The aim of this work was to evaluate whether metalloporphyrin models could mimic the action of cytochrome P-450 in the oxidation of atrazine, a herbicide. The commercially available second-generation metalloporphyrins 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin metal(III) chloride [M(TDCPP)Cl] and 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin metal(III) chloride [M(TFPP)Cl] (metal = Fe or Mn) and the oxidants iodosylbenzene and metachloroperbenzoic acid were employed in this study. Results showed that the metalloporphyrins used here can oxidize atrazine. Yields as high as 32% were obtained for the Mn(TFPP)Cl/PhIO system, which shows that these catalysts can mimic both the in vivo and the in vitro action of cytochrome P-450, with formation of the metabolites DEA and DIA. The formation of five other unknown products was also detected, but only one of them could be identified, since the other four were present in very low concentrations. The compound COA, identified by mass spectrometry, was the main product in most of the oxidation reactions.

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Section: Introductionmentioning

confidence: 99%

Metalloporphyrins as Biomimetic Models for Cytochrome P-450 in the Oxidation of Atrazine

Gotardo

Moraes

Assis

2006

J. Agric. Food Chem.

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“…metalloporphyrines as synthetic livers, can provide a practical tool for generating such libraries. 19 The MeDiverse set of compounds is a selected, diverse library of 10 000 heterocyclic organic compounds. In that collection all possible metabolites are predicted for each member; therefore, it should be considered as an in vivo metabolically extended library.…”

Section: Resultsmentioning

confidence: 99%

“…To model the major biochemical functions, metalloporphyrins have been recently reported as synthetic livers or mimics of the in vivo metabolic processes. 19 Finally in vitro toxicity screening assays are generally cellular based models, allowing estimation of cell toxicity, mutagenicity, and carcinogenicity. Many companies are turning to in vivo multiple cassettes or "n-in-one" dosing strategies, when multiple compounds are administered to a single animal.…”

Section: Early Adme/tox Assessment For Improved Oral Bioavailabilitymentioning

confidence: 99%

Diversity Measures for Enhancing ADME Admissibility of Combinatorial Libraries

Darvas¹,

Dormán²,

Papp³

2000

J. Chem. Inf. Comput. Sci.

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For general screening libraries, structural diversity descriptors and drug-likeness indicators still do not guarantee the in vivo bioavailability for the candidates, which is considered a major bottleneck in drug development. Early prediction of pharmacokinetics (log P, log D), metabolism, and toxicity makes it possible to deal with ADME (adsorption, distribution, metabolism, excretion) related diversity as an extension to the classical diversity concepts. It opens several new possibilities for optimization of a discovery library before doing any experimental screening. This new diversity concept is demonstrated on a subset of MeDiverse, which is a diverse collection of pharmacologically relevant compounds selected from our in-house library. From consideration of the ADME interface in living systems, virtual secondary libraries of metabolites and retrometabolites (prodrugs) can be generated. These additional libraries readily enhance both the structural and ADME related diversity. This new opportunity in library design can substantially improve the success rate for in vivo lead generation from in vitro hits.

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“…3) Among these methods, chemical oxidation by peroxide in the presence of a synthetic iron-porphyrin as a catalyst has been demonstrated to be an effective tool to obtain oxidative degradates for carbamate insecticide, 4) organophosphorus pesticides, 5) insect growth regulator 6) and triazine herbicide. 7) This reaction corresponds to the shunt pathway in CYP450 catalysis to produce the reactive intermediate, oxoiron (IV) porphyrin cation radical, (d) in Fig.…”

Section: Introductionmentioning

confidence: 99%

Iron-Porphyrin catalyzed oxidation of permethrin and fenvalerate

Fukushima

Katagi

2009

J. Pestic. Sci.

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Biomimetic oxidation of a trans isomer of permethrin, fenvalerate, together with the corresponding chrysanthemic acid and alcohol moieties was conducted using catalytic amounts of six iron-porphyrins having different substituents, not only at b-and meso-positions but also the axial ligand of iron in the presence of hydrogen peroxide or meta-chloroperbenzoic acid as an oxidant. The several degradation products via cleavage of ester and ether linkages and hydroxylation were identified and some were found to be in vivo metabolites previously reported in plants, animal and insects. The introduction of electron-withdrawing substituents at b-and mesopositions of a porphyrin ring resulted in higher conversion and the weak electron donor as the axial ligand of iron was found to increase the oxidative reactivity of porphyrin. ©Pesticide Science Society of Japan Keywords: biomimetic oxidation, fenvalerate, iron-porphyrin, permethrin. Materials and Methods Chemicals. trans-Permethrinand their potential degradates were synthesized in our laboratory by the reported methods.9-13) 14 C-I and II were prepared in our laboratory according to the reported procedures 14,15) and their radio-chemical purities were determined to be greater than 98% by HPLC. The specific activity of 14 C-I labeled at 1-position of the cyclopropyl ring and those of 14 C-II uniformly labeled at chlorophenyl and phenoxyphenyl rings were 5.06, 11.2 and 10.5 MBq mg Ϫ1 , respectively. The 14 C-derivatives corresponding to the alcohol moieties, PBalc and PBacid as well as the chrysanthemic acid derivatives of I were prepared during the synthesis of 14 C-I and II. 14 C-labeled CRA was also synthesized by the reported method.16) Abbreviations and the structure of reference standards employed in this study are presented in Table I. Other than the above reference standards, mono-hydroxylated compounds 9,17) of I, II, PBalc, PBacid and t-Cl 2 CA, oxidized compounds at the alkenyl methyl group of CRA 18) , carboxy and amide derivatives of II and dePh-II 13) , 2,3-dihydroxybenzoic acid, 3,5-dihydroxybenzoic acid and phenoxymandelic acid were used for HPLC and TLC analyses, but were not detected and are not listed in Table 1. The six iron porphyrins (Fig. 2) having different substituents at b-and meso-positions of the ring and an axial ligand were used. F 20 TPPFeCl and 4OMeTPPFeCl from Sigma-Aldrich Japan Co., Ltd. (Tokyo, Japan), F 20 Br 8 TPPFeCl from Wako Pure Chemical Industries, Ltd. (Osaka, Japan), and F 20 Br 8 -TPPFeNO 3 and F 20 Br 8 TPPFeCF 3 SO 3 from Funakoshi Co., Ltd. (Tokyo, Japan) were respectively purchased and used without further purification. Cl 8 TPPFeCl was synthesized in our laboratory as reported.19) The apparent valence of iron atom is ϩ3 in all porphyrins. Hydrogen peroxide (H 2 O 2 ) and meta-chloroperbenzoic acid (mCPBA) were purchased from Wako (Japan) and Sigma-Aldrich Japan Co., Ltd. (Tokyo, Japan), respectively, and other reagents were of the purest grade (99%) from Nacalai Tesque, Inc. (Kyoto, Japan). Biomimetic OxidationEach radio...

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Chemical Models of Cytochrome P450 Catalyzed Insecticide Metabolism. Application to the Oxidative Metabolism of Carbamate Insecticides

Cited by 20 publications

References 26 publications

Metalloporphyrins as Biomimetic Models for Cytochrome P-450 in the Oxidation of Atrazine

Metalloporphyrins as Biomimetic Models for Cytochrome P-450 in the Oxidation of Atrazine

Diversity Measures for Enhancing ADME Admissibility of Combinatorial Libraries

Iron-Porphyrin catalyzed oxidation of permethrin and fenvalerate

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