Phenoxyacetic Acid Derivatives Research Articles

Design, Synthesis, Computational Study, and Antidiabetic Evaluation of Benzoxazole Derivatives

AbstractAlpha‐amylase plays a crucial role in blood glucose levels, and thus, its inhibitor can be used to control diabetes. Thus, in vitro alpha‐amylase inhibitory activities were studied for synthesized benzoxazole compounds. The 2‐amino‐benzoxazoles were prepared by reacting 2‐aminophenol with cyanogen bromide, which was coupled with phenoxy acetic acid derivatives (6 a‐n). The compound 6 h was found to be significantly active with IC50 values of 348.43 μg/mL against alpha‐amylase compared to acarbose (IC50=682.54 μg/mL). The molecular docking and molecular dynamic simulation showed better affinity and stability of 6 h at the binding site of the alpha‐amylase protein. Further, a preliminary bioevalauation and antidiabetic study were done through in vivo using SD rats. The efficacy study showed a significant improvement in glucose levels, total cholesterol, triglyceride, LDL, and HDL levels in the compound 6 h and was found to be a lead antidiabetic agent.

Transport of herbicides by PIN-FORMED auxin transporters.

Auxins are a group of phytohormones that control plant growth and development 1. Their crucial role in plant physiology has inspired development of potent synthetic auxins that can be used as herbicides 2. Phenoxyacetic acid derivatives are a widely used group of auxin herbicides in agriculture and research. Despite their prevalence, the identity of the transporters required for distribution of these herbicides in plants is both poorly understood and the subject of controversial debate 3,4. Here we show that PIN-FORMED auxin transporters transport a range of phenoxyacetic acid herbicides across the membrane and we characterize the molecular determinants of this process using a variety of different substrates as well as protein mutagenesis to control substrate specificity. Finally, we present Cryo-EM structures of Arabidopsis thaliana PIN8 with 2,4-dichlorophenoxyacetic acid (2,4-D) or 4-chlorophenoxyacetic acid (4-CPA) bound. These structures represent five key states from the transport cycle, allowing us to describe conformational changes associated with substrate binding and transport across the membrane. Overall, our results reveal that phenoxyacetic acid herbicides use the same export machinery as endogenous auxins and exemplify how transporter binding sites undergo transformations that dictate substrate specificity. These results enable development of novel synthetic auxins and for guiding precision breeding of herbicide resistant crop plants.

Design, Synthesis, and Biological Evaluation of Novel Phenoxy Acetic Acid Derivatives as Selective COX-2 Inhibitors Coupled with Comprehensive Bio-Pharmacological Inquiry, Histopathological Profiling, and Toxicological Scrutiny.

COX-2 plays a key role in converting arachidonic acid into prostaglandins. This makes it a significant target for treating inflammation. Selective COX-2 inhibitors have marked a new phase in inflammatory treatment, providing significant effectiveness while reducing negative side effects. Herein, we aimed at the design and synthesis of new anti-inflammatory agents 5a-f, 7a-b, 10a-f, and 13a-b with expected selective inhibition for COX-2. Compounds 5d-f, 7b, and 10c-f showed significant COX-2 inhibition with IC50 in the range of 0.06-0.09 μM, indicating powerful pharmacological potential. In light of this, eight compounds were selected for further testing in vivo to assess their selectivity toward COX-1/COX-2 enzymes with the ability to reduce paw thickness. Compounds 5f and 7b showed significant anti-inflammatory effects without causing stomach ulcers, as they showed significant in vivo inhibition for paw thickness at 63.35% and 46.51%, as well as paw weight at 68.26% and 64.84%. Additionally, the tested compounds lowered TNF-α by 61.04% and 64.88%, as well as PGE-2 by 60.58% and 57.07%, respectively. Furthermore, these potent compounds were thoroughly analyzed for their pain-relieving effects, histological changes, and toxicological properties. Assessing renal and stomach function, as well as measuring liver enzymes AST and ALT, together with kidney indicators creatinine and urea, offered valuable information on their safety profiles. Molecular modeling studies explain the complex ways in which the strong interacts with the COX-2 enzyme. This comprehensive strategy emphasizes the therapeutic potential and safety profiling of these new analogues for managing inflammation.

Identification of a herbicide-resistant biotype of Echinochloa crus-galli in Ukraine

Ukraine is one of the world’s guarantors of food security and has the potential to further increase agricultural production. However, the vast majority of herbicides used on crops are acetolactate synthase (ALS) inhibitors, which poses a threat of herbicide-resistant weed species. The emergence and spread of herbicide-resistant weed biotypes can significantly increase the cost of growing crops to the point of loss of profitability. Herbicide resistance in barnyardgrass (Echinochloa crus-galli var. crus-galli) has been studied in long-term field and greenhouse experiments. Resistance of E. crus-galli to the ALS herbicide triazolopyrimidine derivative ‒ penoxsulam was identified. Expressed resistance was observed in weed plants grown from seeds collected under production conditions in Kherson region in 2015–2016 and 2020–2021. Cross resistance was observed for imidazolinone and sulfonylurea derivatives. It should be noted that the level of cross resistance to ALS herbicides was slightly higher for plants derived from weed seeds harvested in 2020–2021 compared to those harvested in 2015–2016. The introduction of a herbicidal composition of a herbicide mixture ‒ an inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD) (an enzyme in plants in the chain of carotenoid synthesis) ‒ mesotrione with an ALS-inhibitor (nicosulfuron) allowed effective control of the weed, which indicates the absence of multiple resistance to herbicides ‒ inhibitors of carotenoid synthesis. The high efficiency of E. crus-galli control was established by the application of herbicides ‒ inhibitors of fatty acid synthesis (graminicides). The highest level of efficiency in the experiments was observed with the application of fluazifop-butyl and somewhat less ‒ with pinoxaden. A tendency to reduce phytotoxicity to barnyardgrass from the south of Ukraine was observed with the introduction of tepraloxydim and quizalofop-ethyl. A lower level of phytotoxicity of fenoxaprop-p-ethyl on E. crus-galli should be noted compared to the effect of pinoxaden. No multiple resistance was observed with glyphosate (5-enolpyruvylshikimate-3-phosphate synthase inhibitor) and reglone (photosystem I inhibitor), allowing control of vegetative weeds at the beginning and end of the growing season. It has been established that monocot weed species have significantly increased their presence and harmfulness in agrophytocenoses in Ukraine and in the world since the 1950s with the widespread introduction of selective dicotyledonous species control with aryloxyphenoxyacetic, propionic and benzoic acid derivatives. This trend has been maintained until recently ‒ barnyardgrass is one of the dominant weed species in modern agrophytocenoses of Ukraine. Therefore, the identification of the ALS-resistant biotype of barnyardgrass complicates weed control in the following crops in rotations in the southern regions of the country: in maize crops with cross resistance to nicosulfuron, in sunflower ‒ to imidazolinones (imazamox, imazapyr), and also makes it impossible to use penoxsulam in rice production. Traditionally, the use of synthetic auxins, phenoxyacetic acid derivatives, etc. is used to control ALS-resistance. However, in Kherson region of Ukraine, already in the third year of application of rinskor (florpyrauxifen-benzyl), some weed plants were found on rice fields affected by ALS-resistant barnyardgrass, which recovered after the use of synthetic auxin. Therefore, the control of ALS-resistance (penoxsulam, etc.) in E. crus-galli with the application florpyrauxifen-benzyl in the Kherson region of Ukraine is already limited. An obvious and economically feasible preventive measure against the emergence of resistant weed biotypes is the implementation of GAP (Good Agricultural Practice, FAO) approaches: in particular, the use of high quality seeds without weed impurities, increasing the proportion of agrotechnical weed control measures, restoring and expanding crop rotations with mandatory rotation of herbicides with different modes of action, introducing dicotyledonous/leguminous crops into rotations, and using herbicides with different modes of action in crops separately or in mixtures. At the same time, agrotechnical measures and the preservation of biodiversity in agrophytocenoses should be the main factor in controlling resistance in weeds. The use of herbicides and their mixtures with different modes of action is of secondary importance. The identification of highly damaging ALS-resistant E. crus-galli in southern Ukraine indicates the insufficient effectiveness of weed control exclusively with herbicides with a single mechanism of action and requires a significant revision of the principles of crop rotation and ways of weed control in the country to maintain high levels of profitability and productivity of agrophytocenoses. Solving this problem is urgent for the preservation of Ukraine's potential as one of the guarantors of global food security.

Evaluation of Seven Phenoxyacetic Acid Drifts on Morphological Parameters of Three Rice (Oryza sativa L.) Varieties under Controlled Sowing Conditions in Côte d'Ivoire

Rice, the main food of the population in Côte d'Ivoire, has a low yield. This study aimed to evaluate the ability of phenoxyacetic acid derivatives to boost the vegetative parameters of rice was conducted in Azaguié using a split-plot design. The rice varieties WA638-1, C26, Nérica 2 and seven phenoxyacetic acid derivatives were used. Three rice seeds of each variety were sown in pots. One seedling per variety was de-mated at 7 DAS. Volumes of 150, 180, and 225 ml concentrated at 10-5 M, 10-7 M, and 10-9 M were applied to the leaves on 15, 20, and 25 DAS, respectively. Height, number of tillers, girth and vigor index were determined. The results showed that treatment T7 improved the height of WAB638-1 to 6.75% and tillering to 366.6%. The vigor index was increased to 9.52% by T8 treatment and girth to 80.37% by T20. The formation of C26 tillers was favored at 171% by the T7 treatment, the girth at 83.17% by T21, the vigor index at 10 % by T21 and at 7.50% by the T14 and T8 treatments. In Nérica 2, vigor index and girth were positively induced at 15.15% and 34.83 % by T19 respectively. The vigor index was also promoted at 12.12% by treatments T20 and T21 and the number of tillers was improved at 150% by T13 and T19. As for height, it was stimulated to 22.39 % by the T14 treatment. The height of C26 was reduced except for T12, the vigor index was decreased to 2.50% by treatments T15, T17 and T3, the tillering to 66.70% by T4. The height of WAB638-1 was inhibited to 2.56% with T1 treatments. Treatments T13, T14, T7, T8, T19 and T20 were those that improved the observed parameters.

Evaluation of herbicidal and fungicidal activities of six natural components and their phenoxyacetic acids derivatives and assessment of human health risk posed by oral exposure to them

ABSTRACT In the present study, we isolated linalool, geraniol, carvacrol, thymol, menthol and eugenol; synthesised their phenoxyacetic acid derivatives; and assessed their phytotoxic and genotoxic potentials against weeds and agricultural crops. Moreover, the fungicidal activity of both categories of compounds against 12 fungi was examined. Finally, using probabilistic assessment based on Risk Quotient (RQ) by the Monte Carlo simulation (MCS) method, we examined human health risks via oral exposure to these compounds. Toxic potencies to plants demonstrated that all parameters and related indices including germination percentage, mean germination time, germination rate, root length, shoot length, seedling length and vigour index dose-dependently decreased in both weeds and agricultural crops. Based on the comet assay, DNA damage was observed in the root meristems of the plants. Consequently, a significant decrease was observed in head DNA, whereas a significant increase in tail DNA was observed in response to treatments. Besides, the natural components and semisynthetic molecules showed a broad spectrum of fungicidal traits. However, eugenol and eugenoxyacetic acid inhibitory effects on the growth of the tested fungi were similar to that of benomyl. Our probabilistic health risk assessment indicated di minimis risk for natural components and their phenoxyacetic acid derivatives. Sensitivity analysis showed that concentrations of residues of the compounds had the most significant effect on risk. Current findings could offer a platform for developing sustainable approaches to reduce chemical residues and their consequent risks to the environment and human health.

A synthetic resveratrol analog termed Q205 reactivates latent HIV-1 through activation of P-TEFb

The persistence of HIV-1 latent reservoir creates the major obstacle toward an HIV-1 cure. The “shock and kill” strategy aims to reverse HIV-1 proviral latency using latency-reversing agents (LRAs), thus boosting immune recognition and clearance to residual infected cells. Unfortunately, to date, none of these tested LRA candidates has been demonstrated effectiveness and/or safety in reactivation HIV-1 latency. The discovery and development of effective, safe and affordable LRA candidates are urgently needed for creating an HIV-1 functional cure. Here, we designed and synthesized a series of small-molecule phenoxyacetic acid derivatives based on the resveratrol scaffold and found one of them, named 5, 7-dimethoxy-2-(5-(methoxymethyl) furan-2-yl) quinazolin-4(3H)-one (Q205), effectively reactivated latent HIV-1 in latent HIV-1-infected cells without a corresponding increase in induction of potentially damaging cytokines. The molecular mechanism of Q205 is shown to increase the phosphorylation of the CDK9 T-loop at position Thr186, dissociate positive transcription elongation factor b (P-TEFb) from BRD4, and promote the Tat-mediated HIV-1 transcription and RNA polymerase II (RNAPII) C-terminal domain (CTD) on Ser (CTD-Ser2P) to bind to the HIV-1 promoter. This study provides a unique insight into resveratrol modified derivatives as promising leads for preclinical LRAs, which in turn may help toward inhibitor design and chemical optimization for improving HIV-1 shock-and kill-based efforts.

Linked drug-drug conjugates based on triterpene and phenol structures. Rational synthesis, molecular properties, toxicity and bioactivity prediction

One of the tasks of modern medicinal chemistry is to produce new molecules that have interesting and desired biological effects. In addition, the synthetic procedure for obtaining these compounds should be at least partially smart and rational e.g. “Lego” and green approaches. The study focuses on the synthesis of several hybrid type compounds that are expected to be characterized by beneficial bioactivities. In order to hybridize natural triterpene oleanolic acid and phenol structures, the linker-mode concept was selected. The synthetic goal was achieved in two stages. The first concerns the rapid introduction of the halogenoacidic linker to active phenols selected as a result of microwave-ultrasonic (MW-US) assisted O-alkylation with the use of 2-halogenoacetic acid. The next stage of the synthetic studies involves the reaction of phenoxyacetic acid derivatives obtained containing an active carboxylic group with oleanolic acid/oxime units by the methods typical of triterpene chemistry. Novel linked ester- and iminoester-type triterpene derivatives with phenols (thymol, eugenol, paracetamol, nipagins, naphthols, curcumin and genistein) were obtained and characterized. Additionally, based on the analysis of numerous references and selected methods of computational chemistry (Molinspiration Cheminformatics, Osiris Property Explorer and PASS method) the molecular parameters and the preliminary anti-inflammatory and antinociceptive activity characterising these molecules as potential drugs were calculated and predicted.

Structural, spectroscopic and O–H⋯O hydrogen bonding interaction on monomer and dimer form of hydroxy phenoxy acetic acid derivatives by experimental and computational techniques

Spectral analysis of commercially available cardiovascular drug 4-(hydroxyphenoxy)acetic acid (HPAA) was performed by experimental and theoretical IR, Raman, UV–Vis and NMR techniques.The optimized geometry, wavenumber and intensity of the vibrational bands of a monomer and dimer form of hydroxyphenoxy acetic acid and its related compounds were obtained by the density functional theory (B3LYP) using 6-311 + G(D,P) basis set to reveal the cardiovascular activity of the compound. The most stable conformation of the title compound was carried out by potential energy scan analysis to identify the active sites of the molecule. The natural bond orbital analysis was performed to analyze the activity of the compound. The HOMO-LUMO and MEP analyses were carried out to identify the active part of the molecule. This work was extended to calculate the binding energy and cardiovascular active part of the title compound with suitable protein by Autodock software. The molecular descriptors obtained by the DFT method was used for QSAR model and predicting the cytotoxicity of HPAA. Fingerprint plots and Hirshfeld surfaces were used to locate and analyze the molecular surface and bonding interactions and cardiovascular activity in various methodologies utilized in the establishment of the relative energies. 4-(hydroxyphenoxy)acetic acid was screened for its cardiovascular activity.

Effective removal of calcium and magnesium sulfates from wastewater in the rare earth industry.

The wastewater discharged from the rare earth (RE) industry generally contains a high level of calcium and magnesium sulfates, which confers permanent hardness and causes difficulties in recycling this wastewater. In this study, the alkyl phenoxy acetic acid derivatives including 4-methyl phenoxy acetic acid (M-POAA), 4-tert-butyl phenoxy acetic acid (B-POAA) and 4-tert-octyl phenoxy acetic acid (O-POAA), were synthesized via the Williamson reaction and characterized by nuclear magnetic resonance (NMR), infrared (IR), and ultra-violet (UV) spectroscopy, as well as elemental analysis and X-ray diffraction (XRD). Synthesis of the POAAs were simple and green, and the raw materials used for their production are widely available and low-cost. The potential for removal of Ca and Mg sulfates from industrial wastewater using POAAs as the organic precipitants was assessed. The total precipitation efficiencies of Ca and Mg from wastewater with the use of POAAs increased with the following order: M-POAA < B-POAA < O-POAA. The residual concentrations of Ca and Mg using O-POAA as the precipitant were lower than 0.099 and 0.089 g L−1, respectively. The O-POAA could be regenerated five times without any significant change in its structure and precipitation performance. Thus, the use of the novel precipitants is a prospective alternative to the conventional processes for softening wastewater.

Design, synthesis and biological activity of phenoxyacetic acid derivatives as novel free fatty acid receptor 1 agonists

The free fatty acid receptor 1 (FFA1) is a novel antidiabetic target for the treatment of type 2 diabetes based on particular mechanism in amplifying glucose-stimulated insulin secretion. We have previously identified a series of phenoxyacetic acid derivatives. Herein, we describe the further chemical modification of this series directed by ligand efficiency and ligand lipophilicity efficiency. All of these efforts lead to the discovery of the promising candidate 16, an excellent FFA1 agonist with robust agonistic activity (43.6nM), desired LE and LLE values. Moreover, compound 16 revealed a great potential for improving the hyperglycemia levels in both normal and type 2 diabetic mice without the risk of hypoglycemia even at the high dose of 40mg/kg.

Synthesis and biological evaluation of phenoxyacetic acid derivatives as novel free fatty acid receptor 1 agonists

Free fatty acid receptor 1 (FFA1) is a new potential drug target for the treatment of type 2 diabetes because of its role in amplifying glucose-stimulated insulin secretion in pancreatic β-cell. In the present studies, we identified phenoxyacetic acid derivative (18b) as a potent FFA1 agonist (EC50=62.3nM) based on the structure of phenylpropanoic acid derivative 4p. Moreover, compound 18b could significantly improve oral glucose tolerance in ICR mice and dose-dependently reduced glucose levels in type 2 diabetic C57BL/6 mice without observation of hypoglycemic side effect. Additionally, compound 18b exhibited acceptable PK profiles. In summary, compound 18b with ideal PK profiles exhibited good activity in vitro and in vivo, and might be a promising drug candidate for the treatment of diabetes mellitus.

Synthesis and in-vivo hypolipidemic activity of some novel substituted phenyl isoxazol phenoxy acetic acid derivatives

The present study was undertaken to evaluate in-vivo hypolipidemic activity of a novel series of 2-methyl-2-(substituted phenyl isoxazol)phenoxyacetic acid derivatives by triton induced hyperlipidemia in rats. The newly synthesized compounds 5a, 5d and 5g showed significant decrease in the serum TCH, TG, LDL and VLDL along with an increase in serum HDL levels as compared to standard drug Fenofibrate. The treated groups also showed significant decrease in the atherogenic index and increase in % protective activity compared to control group.

Correlations between Chromatographic Parameters and Bioactivity Predictors of Potential Herbicides

Different liquid chromatography techniques, including reversed-phase liquid chromatography on Purosphere RP-18e, IAM.PC.DD2 and Cosmosil Cholester columns and micellar liqud chromatography with a Purosphere RP-8e column and using buffered sodium dodecyl sulfate-acetonitrile as the mobile phase, were applied to study the lipophilic properties of 15 newly synthesized phenoxyacetic and carbamic acid derivatives, which are potential herbicides. Chromatographic lipophilicity descriptors were used to extrapolate log k parameters (log kw and log km) and log k values. Partitioning lipophilicity descriptors, i.e., log P coefficients in an n-octanol-water system, were computed from the molecular structures of the tested compounds. Bioactivity descriptors, including partition coefficients in a water-plant cuticle system and water-human serum albumin and coefficients for human skin partition and permeation were calculated in silico by ACD/ADME software using the linear solvation energy relationship of Abraham. Principal component analysis was applied to describe similarities between various chromatographic and partitioning lipophilicities. Highly significant, predictive linear relationships were found between chromatographic parameters and bioactivity descriptors.

Effect of structurally constrained oxime–ether linker on PPAR subtype selectivity: Discovery of a novel and potent series of PPAR-pan agonists

A novel series of thaizole and oxazole containing phenoxy acetic acid derivatives is reported as PPAR-pan agonists. Incorporation of structurally constrained oxime-ether based linker in the chemotype of a potent PPARδ selective agonist GW-501516 was adapted as designing strategy. In vitro, selected test compounds 12a, 12c, 17a and 18a showed PPAR-pan agonists activities and among these four compounds tested, 12a emerged as highly potent and efficacious compound, while 17a exhibited moderate and balanced PPAR-pan agonistic activity. In vivo, selected test compounds 12a and 17a exhibited significant anti-hyperglycemic and anti-hyperlipidemic activities in relevant animal models. These results support our hypothesis that the introduction of structurally constrained oxime-ether linker between lipophilic tail and acidic head plays an important role in modulating subtype selectivity and subsequently led to the discovery of potent PPAR-pan agonists.

Hypolipidaemic and antiplatelet activity of phenoxyacetic acid derivatives related to α-asarone

The phenoxyacetic acid derivatives 1-6 [2-methoxy-4-(2-propenyl)phenoxyacetic acid (1); 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid (2); methyl 2-methoxy-4-(2-propenyl)phenoxyacetate (3); ethyl 2-methoxy-4-(2-propenyl)phenoxyacetate (4); methyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (5); ethyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (6)] related to alpha-asarone have been reported previously as hypolipidaemic agents in diet-induced hyperlipidaemic mice. We have aimed to expand the pharmacological profile of these derivatives by investigating their hypolipidaemic activity in rats and mice under different experimental conditions. The antiplatelet activity was tested also in-vitro from blood derived from consenting healthy volunteers. In normolipidaemic rats, compounds 2, 3 and 5 at oral doses of 40 and 80 mg kg(-1) significantly decreased total cholesterol and LDL-cholesterol levels. Moreover, analogues 3 and 5 administered to hypercholesterolaemic rats at the same doses for seven days also produced a reduction in the content of these same lipoproteins. In neither case were the high-density lipoprotein cholesterol and triglyceride concentrations affected. However, practically all tested compounds were found to be hypocholesterolaemic agents, and were shown to effectively lower low-density lipoprotein cholesterol and triglyceride levels in Triton-induced hyperlipidaemic mice at oral doses of 50 and 100 mg kg(-1). In all tests, all animals appeared to be healthy throughout the experimental period in their therapeutic ranges. Triton-induced hypercholesterolaemic mice appeared to be a desirable model for this class of hypolipidaemic drugs. On the other hand, compounds 1, 2, 4 and 5 significantly inhibited ADP-induced aggregation in-vitro. These findings indicated that all of these compounds appeared to be promising for the treatment of human hyperlipidaemia and thrombotic diseases.

Synthesis and evaluation of in vitro antiviral activity of novel phenoxy acetic acid derivatives

Several substituted phenoxy acetic acid derived pyrazolines were synthesized by the reaction between 2-{4-[3-(2,4-dihydroxyphenyl)-3-oxo-1-propenyl]-2-methoxyphenoxy} acetic acid and substituted acid hydrazides and were tested for their in vitro cytotoxicity and antiviral activity. None of the compounds showed any specific antiviral activity [50% antivirally effective concentration (EC50) ≥ 5-fold lower than minimum cytotoxic concentration]. The most cytotoxic of the series was 2-{4-[3-(2,4-dihydroxyphenyl)-1-(2-hydroxybenzoyl-4,5-dihydro-1H-5-pyrazolyl]-2-methoxyphenoxy}acetic acid (3j), with a minimum cytotoxic concentration of 0.16 μg/mL in human embryonic lung (HEL) cells.

Uptake of phenoxyacetic acid derivatives into Caco-2 cells by the monocarboxylic acid transporters

The uptake mechanism of phenoxyacetic acid (PA) and its chlorine derivatives, 4-chlorophenoxyacetic acid (4-CPA), 2,4-dichlorophenoxyacetic acid (2,4-D), and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), was investigated using Caco-2 cells. The cells were incubated with PA, 4-CPA, 2,4-D or 2,4,5-T at pH 6.0 and 37 degrees C. The order of uptake and lipophilicity expressed by n-octanol partition coefficients were PA<4-CPA<2,4-D<2,4,5-T. Incubation at 4 degrees C or at pH 7.4 significantly decreased these uptake. Furthermore, pretreatment with the protonophore, carbonylcyanide-p-(trifluoromethoxy) phenylhydrazone, or coincubation with benzoic acid, a typical substrate for the proton-linked monocarboxylic acid transporters (MCTs), significantly decreased the uptake of all compounds. The initial uptake rates of all compounds except PA were apparently saturable, suggesting the involvement of a carrier-mediated process. The order of uptake clearance of the compounds was the same as the order of their uptake and lipophilicity. Preloading of cells with benzoic acid significantly increased their uptake except for PA. These results suggest that the uptake of PA, 4-CPA, 2,4-D and 2,4,5-T from the apical membrane of Caco-2 cells is mediated via common MCTs shared, at least in part, with benzoic acid, and the increase in lipophilicity due to the chlor-substitution may increase uptake via the MCTs.

Selection of sorbent for removing pesticides during water treatment

This paper presents research on phenoxyacid pesticides removal using sorption methods on activated carbons. It was noted, that physico-chemical properties of adsorbent and adsorbate as well as parameters of the process have influence on adsorption of pesticides, derivatives of phenoxyacetic acid on carbon. The experimental data were analyzed by the Freundlich isotherm. The best for remove from water on carbon NP-5 was 2,4-D. Equilibrium data fitted well with the Freundlich model with maximum adsorption capacity of NP-5 carbon. The exemplary sorption capacity at equilibrium concentration 10 mg L −1 were: 2,4-D 70 mg g −1, MCPA 2 mg g −1, MCPP 0.5 mg g −1. The results indicated that coconut shell-based NP-5 carbon is most effective for the adsorption of phenoxyacetic acid from aqueous solutions.

QSAR study of 2,4-disubstituted phenoxyacetic acid derivatives as a CRTh2 receptor antagonists

AbstractIn pursuit of better CRTh2 receptor antagonist agents, QSAR studies were performed on a series of 2,4-disubstituted phenoxyacetic acid derivatives. Stepwise multiple linear regression analysis was performed to derive QSAR models which were further evaluated for statistical significance and predictive power by internal and external validation. The best QSAR model was selected; having the correlation coefficient R = 0.904, standard error of estimation SEE = 0.456 and the cross validated squared correlation coefficient Q 2 = 0.739. Predictive ability of the selected model was also confirmed by the leave one out cross validation method and by leave 33 % out Q 2 = 0.688. The QSAR model indicates that the descriptors (logP, SI3, LM, and DVZ) play an important role in the CRTh2 receptor antagonist activities. Results of the present study may be useful in the designing of more potent 2,4-disubstituted phenoxyacetic acid derivatives as CRTh2 receptor antagonist agents.