Enantioselective Effects Research Articles

Enantioselective Oxidative Stress Induced by S- and Rac-metolachlor in Wheat (Triticum aestivum L.) Seedlings.

The unfounded use of chiral pesticides has caused widespread concern. In this study, the enantioselective effects of S- and racemic (Rac)-metolachlor on the oxidative stress of wheat seedlings was determined based on physiological and gene transcription differences. Growth inhibition increased with increasing concentrations of tested metolachlor, and S-metolachlor had a stronger inhibitory effect than did Rac-metolachlor. Root growth was also significantly inhibited, but no enantioselective effects from the tested concentrations of the metolachlor enantiomers were observed. At a concentration of 5mgL-1, the maximal fresh weight inhibition reached 63.7% and 53.8% for S-metolachlor and Rac-metolachlor, respectively. In response to the S-metolachlor treatment, the maximum level of superoxide anions and malondialdehyde (MDA) increased to 1.73 and 2.55 times that in response to the control treatment, both of which were greater than those in response to the Rac-metolachlor treatment. The activity of superoxide dismutase (SOD) also increased in response to the S-metolachlor treatment, but the activity of peroxidase (POD) decreased. Real-time polymerase chain reaction (PCR) revealed that, compared with the Rac-metolachlor treatment, the S-metolachlor treatment attenuated the expression of several antioxidant genes. Together, these results demonstrate that S-metolachlor has a greater effect than does Rac-metolachlor on wheat seedlings.

Microbial transformation of chiral organohalides: Distribution, microorganisms and mechanisms.

Chiral organohalides including dichlorodiphenyltrichloroethane (DDT), Hexabromocyclododecane (HBCD) and polychlorinated biphenyls (PCBs) raise a significant concern in the environmental occurrence, fate and ecotoxicology due to their enantioselective biological effects. This review provides a state-of-the-art overview on enantioselective microbial transformation of the chiral organohalides. We firstly summarized worldwide field assessments of chiral organohalides in a variety of environmental matrices, which suggested the pivotal role of microorganisms in enantioselective transformation of chiral organohalides. Then, laboratory studies provided experimental evidences to further link enantioselective attenuation of chiral organohalides to specific functional microorganisms and enzymes, revealing mechanistic insights into the enantioselective microbial transformation processes. Particularly, a few amino acid residues in the functional enzymes could play a key role in mediating the enantioselectivity at the molecular level. Finally, major challenges and further developments toward an in-depth understanding of the enantioselective microbial transformation of chiral organohalides are identified and discussed.

Enantioselective Toxicity of Chiral Herbicide Metolachlor to Microcystis aeruginosa.

The enantioselective effects of chiral herbicides on aquatic organisms have received increasing attention. As one kind of freshwater algae responsible for most algal blooms, Microcystis aeruginosa can produce hepatotoxic microcystin and cause serious health concerns for drinking water. Thus, the effects of chiral herbicides on M. aeruginosa are of vital significance but poorly understood, especially as the structures of chiral herbicides become more complex. In this study, the enantioselective effects of four metolachlor enantiomers based on carbon center and axis chirality on M. aeruginosa were investigated for the first time at an enantiomeric level. The results of the investigation into algal growth inhibition, chlorophyll a content, and cell integrity indicated that ( S)-metolachlor [( S)-Met] was significantly more toxic than any other isomer. The toxicity ranking of different enantiomers at the highest concentration (15 mg/L) against M. aeruginosa was ( S)-Met > (α R,1' S)-Met > (α S,1' S)-Met > (α S,1' R)-Met > (α R,1' R)-Met, with (α S,1' S)-Met and (α R,1' S)-Met displaying a synergistic effect. Additionally, the Fe distribution in M. aeruginosa presented distinct enantioselectivity, which may contribute to the enantioselective toxicity of metolachlor. Furthermore, metolachlor upregulated the expression of genes mcyD and mcyH in an enantioselective manner, indicating that this herbicide can potentially promote the synthesis and efflux of microcystin, thus aggravating agricultural water contamination to different extents. Overall, this study will help to understand the ecotoxicity of metolachlor at a deeper level and provide theoretical insights into the enantioselective behaviors of metolachlor.

Enantioselective effects of the chiral fungicide tetraconazole in wheat: Fungicidal activity and degradation behavior

Tetraconazole, a chiral triazole fungicide, is widely used for the prevention of plant disease in wheat fields. However, the chirality of pesticides like tetraconazole can cause diverse biological responses. Therefore, it is important that research is conducted to investigate the enantioselective effects of chiral enantiomers in this regard. The absolute configurations of two tetraconazole enantiomers were initially confirmed by ECD (Electrostatic circular dichroism). The bioassay test showed that the fungicidal activity of (R)-(+)-tetraconazole against two pathogens (R. cerealis and F. graminearum) was approximately 1.49–1.98 times greater than that for (S)-(−)- tetraconazole. Following recovery experiments, a modified QuEchERS (Quick, easy, cheap, effective, rugged, safe) method was established using UPLC-MS/MS (ultra-performance liquid chromatography tandem mass spectrometry). The mean recoveries from plant and soil sample ranged from 78.9% to 100.5% with intraday relative standard (RSDr) values of 0.8%–6.9% and interday relative standard (RSDR) values of 3.0%–5.2% respectively. The stereoselective degradation of tetraconazole in wheat meant that (S)-(−)-tetraconazole was more rapidly degraded than (R)-(+)-tetraconazole. Conversely, (R)-(+)-tetraconazole was preferentially degraded in wheat soil. These results will provide us with a greater understanding when assessing future environmental risk assessments and strategies that invoke pesticide reduction.

Enantioselective effect of glufosinate on the growth of maize seedlings.

Glufosinate is a non-selective chiral herbicide, which has been used extensively around the world. However,limited information on the enantioselectivity of Rac- and L-glufosinate against crops. In this study, the enantioselective effects on the growth, antioxidant, and targeted enzyme activities of maize seedlings of chiral glufosinate were investigated. The results showed the enantioselective growth inhibitions were observed at both 1 and 5mg/L concentration levels. L-Glufosinate induced more growth rate reduction in shoot height and weight compared to Rac-glufosinate. All of the antioxidant enzyme activities increased obviously in the leaves of maize seedlings treated by 1mg/L of glufosinate. Superoxide dismutase (SOD) activity, catalase (CAT) activity, peroxidase (POD) activity, glutathione reductase (GR) activity, and malondialdehyde (MDA) content induced by L-glufosinate were 1.36, 1.16, 1.51, 1.65, and 1.65 times higher than those by Rac-glufosinate, respectively Notably, the glutamine synthetase (GS) activity was significantly reduced to 80% and 57% in the control group at 1mg/L treated with Rac- and L-glufosinate, respectively. Our results indicated that Rac- and L-glufosinate showed the obvious enantioselectivity in the growth of maize seedlings, which has shed light on the potential enantioselective phytotoxicity of glufosinate. Data provided here will be helpful to develop the environmentally friendly herbicides.

Enantioselective Dechlorination of Polychlorinated Biphenyls in Dehalococcoides mccartyi CG1.

Reductive dehalogenation mediated by organohalide-respiring bacteria plays a critical role in the global cycling of organohalides. Nonetheless, information on the dehalogenation enantioselectivity of organohalide-respiring bacteria remains limited. In this study, we report the enantioselective dechlorination of chiral polychlorinated biphenyls (PCBs) by Dehalococcoides mccartyi CG1. CG1 preferentially removed halogens from the (-)-enantiomers of the three major environmentally relevant chiral PCBs (PCB174, PCB149, and PCB132), and the enantiomer compositions of the dechlorination products depended on their parent organohalides. The in vitro assays with crude cell extracts or concentrated whole cells and the in vivo experiments with living cells showed similar enantioselectivities, in contrast with the distinct enantiomeric enrichment factors (εER) of the substrate chiral PCBs. Additionally, these results suggest that concentrated whole cells might be an alternative to crude cell extracts in in vitro tests of reductive dehalogenation activities. The enantioselective dechlorination of other chiral PCBs that we resolved via gas chromatography further confirmed the preference of CG1 for the (-)-enantiomers.IMPORTANCE A variety of agrochemicals and pharmaceuticals are chiral. Due to the enantioselectivity in biological processes, enantiomers of chiral compounds may have different environmental occurrences, fates, and ecotoxicologies. Many chiral organohalides exist in anaerobic or anoxic soils and sediments, and organohalide-respiring bacteria play a major role in the environmental attenuation and global cycling of these chiral organohalides. Therefore, it is important to investigate the dehalogenation enantioselectivity of organohalide-respiring bacteria. This study reports the discovery of enantioselective dechlorination of chiral PCBs by Dehalococcoides mccartyi CG1, which provides insights into the dehalogenation enantioselectivity of Dehalococcoides and may shed light on future PCB bioremediation efforts to prevent enantioselective biological side effects.

Neolignans from Red Raspberry ( Rubus idaeus L.) Exhibit Enantioselective Neuroprotective Effects against H2O2-Induced Oxidative Injury in SH-SY5Y Cells.

Red raspberry has been well-known for its nutritional purpose. Although this fruit has been reported for its potent antioxidant activity and health-promoting properties, systematic studies responsible for the bioactive constituents were still insufficient. In the current study, three pairs of dihydrobenzofuran-type enantiomeric neolignans (1a/1b-3a/3b), including two new compounds (1b and 2a), were isolated from the fruit of Rubus idaeus. The structures of these enantiomers were determined through spectroscopic methods and quantum mechanical calculations. Biologically, enantiomers 2a and 2b exhibited significant enantioselective protective effects against H2O2-induced neurotoxicity at 50 μM (2a, 86.72 ± 1.17%; 2b, 69.70 ± 1.59%). The underlying mechanism study demonstrated that enantiomer 2a is able to attenuate H2O2-induced apoptosis, reactive oxygen species (ROS) generation, and mitochondrial dysfunction in SH-SY5Y cells. Overall, these findings provide a valuable foundation for the understanding of neuroprotective activities of red raspberry and further investigation on its potential application values.

Enantioselective toxic effects and environmental behavior of ethiprole and its metabolites against Chlorella pyrenoidosa

Insecticide ethiprole, the alternative of fipronil which has been restricted in many countries, may contaminant water bodies through surface runoff after agricultural application, however, the aquatic toxicity and environmental behavior of ethiprole is still unknown. In this study, five metabolites of ethiprole (ethiprole sulfone, ethiprole sulfide, ethiprole amide, desethylsulfinyl ethiprole and ethiprole sulfone amide) were synthesized and their toxic effects on photosynthetic pigment and antioxidase in aquatic plant Chlorella pyrenoidosa (C. pyrenoidosa) were evaluated on an enantiomeric level. Besides, the accumulation and metabolism of rac-ethiprole and its enantiomers in algae suspension and algae were studied. Ethiprole sulfide was found to be more toxic than ethiprole, with the 96h EC50 value seven times lower than ethiprole. Enantioselective toxicity was observed with R-ethiprole more toxic than S-ethiprole. The contents of chlorophyll were significantly reduced by all the chemicals at higher concentrations, and the levels of protein, malondialdehyde (MDA) and the activity of antioxidant defense enzymes were dose-dependent. The half-life of rac-ethiprole in algae suspension was 13.6 days and ethiprole amide was the major metabolite. However, ethiprole sulfide was the main metabolite in algae, suggesting different metabolic pathways in algae suspension and algae. Enantioselective metabolism in algae suspension was found with S-ethiprole metabolized faster than R-ethiprole. The preferentially accumulated and metabolized of R-ethiprole in algae was observed and C. pyrenoidosa had limited capacity to convert one enantiomer into the other. These findings indicated the toxicity of ethiprole to C. pyrenoidosa is lower than fipronil. The individual enantiomers of chiral pollutants and their metabolites should be considered in risk assessments.

Enantioselective toxic effects of cyproconazole enantiomers against Rana nigromaculata

The environmental contaminant, especially pesticides, threatened the amphibian population. In this assay, the enantioselective behavior of cyproconazole on Rana nigromaculata was studied. We found LC50 (lethal concentration causing 50% mortality) of 4-enantiomers was nearly twice as 3-enantiomers in 96 h acute toxicity test. Besides, the significant considerable variation of oxidative stress and LDH (lactic dehydrogenase) induced by the four enantiomers indicated that cyproconazole could enantioselectively affect enzymes in tadpoles. Bioaccumulation experiments showed the order of cyproconazole in the tadpoles was 4-enantiomers>3- enantiomers>2- enantiomers>1- enantiomers during the exposure for 28d. In tissue distribution test, cyproconazole was formed and accumulated in order of 4-enantiomers>2-enantiomers>3- enantiomers>1- enantiomers, except that in the gut. During the elimination experiment, cyproconazole was rapidly eliminated by 95% within the only 24 h. These results suggested that the influence of enantioselective behavior should consider when assessing ecological risk of chiral pesticides to amphibians.

Enantioselective toxic effects and digestion of furalaxyl enantiomers in Scenedesmus obliquus.

Research on the enantioselective environmental behavior of chiral pesticides has been a hot spot of environmental chemistry recently. In this study, the acute toxicity and digestion of furalaxyl enantiomers were determined on the aquatic algae Scendesmus obliquus. After exposure for 96hours, the EC50 values for (S)-furalaxyl and (R)-furalaxyl were 13.59 and 15.26mg/L, respectively. In addition, enantioselectivity was observed from the determined chlorophyll contents and antioxidant enzyme (CAT and SOD) activities of algae cells after exposure to furalaxyl enantiomers for 96hours. The digestion rate of (S)-furalaxyl and (R)-furalaxyl were almost the same in S. obliquus. On the basis of these data, the inactive enantiomers (S)- furalaxyl is more toxic than the active one on the non-target species S. obliquus, indicating that such enantiomeric differences should be taken into consideration in the study of pesticide risk assessment.

Enantioselective bioaccumulation and metabolism of lactofen in zebrafish Danio rerio and combined effects with its metabolites

Pesticide residue in agricultural land might led to contamination of fresh waters, creating potential risks to organisms. The environmental behavior of herbicide lactofen may be enantioselective and the metabolites may have high toxic effects in individual or in combination. In this work, the enantioselective bioaccumulation, metabolism and toxic effects of lactofen and three metabolites (desethyl lactofen, acifluorfene, and amino acifluorfene) in zebrafish were investigated. The antioxidase activity (superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase), lipid peroxidation content were measured after exposure, and genetic toxicity was evaluated by a micronucleus test. The integrated biomarker response (IBR) method was used to determine the effects of the lactofen and its metabolites as well as their combinations. The metabolites were found to have higher toxic effects, and enantioselective toxic effects of lactofen and desethyl lactofen were observed, with the S-enantiomer more toxic. Based on IBR values, synergistic effects existed in combination of lactofen and desethyl lactofen, while antagonistic effects of lactofen with acifluorfene or amino acifluorfene were observed. Zebrafish were exposed to 0.5 mg L−1 lactofen and the bioaccumulation were measured during a 15 d period followed by a 7 d elimination. The half-lives of the metabolites varied between 0.66 and 5.21 d, with bioconcentration factors (BCFs) in the range of 39–120. The metabolic pathways of R- and S-lactofen were found to be significantly different. The results supported our hypothesis. Therefore, the assessment of enantiomers and metabolites in individual or in combination should be taken into consideration in evaluating chiral pesticide risks.

Enantioselective Effects of Metalaxyl Enantiomers in Adolescent Rat Metabolic Profiles Using NMR-Based Metabolomics.

More than 30% of the registered pesticides are chiral with one or more chiral centers and exist as two or more enantiomers. The frequency of chiral chemicals and their environmental safety has been considered in their risk assessment in recent decades. Despite the fact that metabolic disturbance is an important sensitive molecular initiating event of toxicology effects, the potential mechanisms of how chiral compounds affect metabolism phenotypes in organisms remain unclear. As a typical chiral pesticide, metalaxyl is an acylalanine fungicide with systemic function. Although the fungicidal activity almost comes from the R-enantiomer, the toxicity of both enantiomers in animals and human beings is not yet clear. In this study, a nuclear magnetic resonance (NMR)-based metabolomics approach was adopted to evaluate the enantioselectivity in metabolic perturbations in adolescent rats. On the basis of multivariate statistical results, stable and evident metabolic profiles of the enantiomers were obtained. When rats were exposed to R-metalaxyl, the significantly perturbed metabolic pathways were biosynthesis of valine, leucine, and isoleucine, synthesis and degradation of ketone bodies, and metabolism of glycerolipid. In contrast, more significantly perturbed metabolic pathways were obtained when the rats were exposed to S-metalaxyl, including glycolysis, biosynthesis of valine, leucine, and isoleucine, metabolism of glycine, serine, and threonine, synthesis and degradation of ketone bodies, metabolism of glycerophospholipid and glycerolipid. These abnormal metabolic pathways were closely related to liver metabolism. These results offer more detailed information about the enantioselective metabolic effects of metalaxyl in adolescent development and provide data for the health risk assessment of metalaxyl at molecular level.

Enantioselective Complexation of Chiral Oxirane Derivatives by an Enantiopure Cryptophane in Water

We show here that optically active cryptophane 1 bearing phenol functions can efficiently bind the two enantiomers of 2‐(chloromethyl)oxirane, ethyloxirane, and 2,2′‐bioxirane derivatives in aqueous solution. The binding process is characterized by high‐field 1H NMR signals that are specific to the encapsulated species. In all cases, an enantioselective effect was observed and a relationship between the molecular volume of the guest and the binding constant can be established, even though the flexibility of the guest molecule also seems to play a role. In this series, the 2,2′‐bioxirane guest is a particularly interesting example, because this compound possesses two stereogenic centers. Thus, in solution, three different pairs of enantiomers can be obtained in the presence of the optically active host 1. Electronic circular dichroism (ECD) spectroscopy has also been used to characterize these complexes; specific ECD spectra recorded in the 1Lb region were obtained for each diastereomer.

Stability, lability, spectral parameters and structure of complexes and stereoselective effects in the nickel(II) – l/d/dl-histidine – l/d/dl-methionine systems

Abstract The equilibrium constants, spectral characteristics of complexes, formation thermodynamic parameters and constants of the chemical exchange reactions in the nickel(II) – l / d / dl -histidine (HisH) – l / d / dl -methionine (MetH) systems (25 °C, 1.0 mol dm−3 KNO3) over wide ranges of pH and ligands to metal ratio were calculated from the pH-potentiometry, multi-wavelength electronic spectroscopy, calorimetry and NMR relaxation data. Based on the DFT computation the structures of some complexes have been proposed. Significant enantioselective effects are exhibited in the formation constants and in some electronic spectra and NMR relaxation parameters of a number of complexes with the meso-forms domination. For the Ni(His)2 complex the process of alkaline catalysis of proton exchange with the short-time N-H proton removal from the coordinated imidazole fragment was characterized. It was shown that in the ligand exchange reaction between Ni(His)2 and His− the Ni(His)3− complex participates as an intermediate. It was found that the Met− thiomethyl group is not bounded in the Ni(Met)+ and Ni(Met)2 complexes but coordinated in the Ni(His)(Met) form. Main factors determining stereoselectivity in the complex formation processes and ligand exchange reactions in the systems studied were identified as trans effect, solvation effect and a new type of interligand thiomethyl group–imidazole ring weak interaction.

Enantioselective effects of chiral amide herbicides napropamide, acetochlor and propisochlor: The more efficient R-enantiomer and its environmental friendly

Amide herbicides, which are used extensively worldwide, are often chiral. Enantiomeric selectivity comes from the different effects of the enantiomers on target and non-target organisms. In this study, the enantiomers of three amide herbicides were purified by the semi-preparative column and were used to investigate the enantioselective effects on target Echinochloa crusgalli (lowland rice weeds), and non-target Microcystis aeruginosa, and the yeast transformed with the human TRβ plasmid organisms. The results showed that (i) the R-enantiomers of the three amide herbicides exhibited the strongest activity toward weed inhibition and the lowest toxicity toward non-target organisms; (ii) napropamide was better suited for controlling root growth, while acetochlor and propisochlor were better for leaves control; (iii) herbicides at certain low concentrations (0.01 mg L−1 for acetochlor and propisochlor) could be utilized to promote plant growth. These findings encourage the use of R-amide herbicides instead of their racemates to increase the efficiency of weed control and reduce the risk to non-target organisms. On the other hand, the adverse effects are caused mostly by S-enantiomer, using R-enantiomer-enriched products may offer great environmental/ecological benefits.

Selective effect of myclobutanil enantiomers on fungicidal activity and fumonisin production by Fusarium verticillioides under different environmental conditions

Myclobutanil is a widely used triazole fungicide, comprising two enantiomers with different fungicidal activities, non-target toxicities, and environmental fates. The enantioselective effects of myclobutanil on fumonisin B (FB) production by Fusarium verticillioides, an important pathogen, have not yet been investigated. In the present study, the fungicidal activities of rac-myclobutanil and its enantiomers on F. verticillioides cultured on maize-based media were studied under different water activity and temperature conditions. The FB levels were measured to assess the enantioselective effects on FB production when F. verticillioides were cultured treated with EC50 and EC90 concentrations (concentrations inhibiting mycelial growth by 50.0% and 90.0%, respectively) of myclobutanil and enantiomers under different conditions. The fungicidal activities of rac-myclobutanil and its enantiomers decreased with increasing temperature and decreasing water activity. Little difference in fungicidal activity was observed between the enantiomers. FB production was significantly influenced by temperature, aw, and fungicides dose. At EC50 concentrations, rac-myclobutantil and its enantiomers were shown to enhance mycotoxin production and enantioselective effects of enantiomers on FB production were observed under certain conditions. This is the first report on the differential effects of myclobutanil enantiomers on the control of F. verticillioides growth and FB production in maize-based media under different conditions.

Occurrence of Chiral Bioactive Compounds in the Aquatic Environment: A Review

In recent decades, the presence of micropollutants in the environment has been extensively studied due to their high frequency of occurrence, persistence and possible adverse effects to exposed organisms. Concerning chiral micropollutants in the environment, enantiomers are frequently ignored and enantiomeric composition often neglected. However, enantioselective toxicity is well recognized, highlighting the need to include enantioselectivity in environmental risk assessment. Additionally, the information about enantiomeric fraction (EF) is crucial since it gives insights about: (i) environmental fate (i.e., occurrence, distribution, removal processes and (bio)degradation); (ii) illicit discharges; (iii) consumption pattern (e.g., illicit drugs, pharmaceuticals used as recreational drugs, illicit use of pesticides); and (iv) enantioselective toxicological effects. Thus, the purpose of this paper is to provide a comprehensive review about the enantioselective occurrence of chiral bioactive compounds in aquatic environmental matrices. These include pharmaceuticals, illicit drugs, pesticides, polychlorinated biphenyls (PCBs) and polycyclic musks (PCMs). Most frequently analytical methods used for separation of enantiomers were liquid chromatography and gas chromatography methodologies using both indirect (enantiomerically pure derivatizing reagents) and direct methods (chiral stationary phases). The occurrence of these chiral micropollutants in the environment is reviewed and future challenges are outlined.

Enantioselective disturbance of chiral herbicide dichlorprop to nitrogen metabolism of Arabidopsis thaliana: Regular analysis and stable isotope attempt

As the most essential element, nitrogen play a pivotal role in plant physiological process, which is susceptible to contaminants. However, the enantioselective effects of chiral herbicides on nitrogen metabolism have not been comprehensively understood. In this study, effects of chiral herbicide dichlorprop (DCPP) on the nitrogen behaviors in Arabidopsis thaliana were investigated. The results revealed that the uptakes of inorganic nitrogen (NO3− and NH4+) were preferentially impacted by herbicidal active (R)-DCPP, where the transportation of beneficial NO3− was inhibited but the toxic NH4+ was accumulated. As for nitrogen assimilation, enantioselectivity was disappeared and reoccurred when NO3− was assimilated into NH4+. Furthermore, the pathways of NH4+ assimilation differed in Arabidopsis exposed to DCPP enantiomers, where (S)-DCPP remained almost the same to the control relying on GS-GOGAT cycle, but the dominant pathway in (R)-DCPP group was shifted to glutamate dehydrogenase route. Consequently, a profound enantioselectivity was also observed in the effects on amino acids synthesis. As for nitrogen stable isotope fractionation, (R)-DCPP led to more negative δ15N values than (S)-DCPP at 0.3μM, indicating the selective uptake of toxic NH4+ and different discrimination of δ15N was also observed between DCPP enantiomers. Moreover, stable isotopic evidence also revealed the disturbance caused by DCPP to the balance of nitrogen demand and consumption in A. thaliana. All these results may contribute to the final enantioselective toxicity, providing a new sight into the better understanding the action mechanism of chiral herbicides.

The enantioselective toxicity and oxidative stress of beta-cypermethrin on zebrafish

Although the toxicity of beta-cypermethrin (beta-CYP) to aquatic organisms has become a significant concern in recent years, its enantioselective effects on non-target organisms is poorly understood. To investigate the enantioselective toxicity of beta-CYP on zebrafish, adult zebrafish were exposed to a series of isometric concentrations of four beta-CYP enantiomers and the beta-CYP racemate for 96 h. In addition, the activities of four antioxidant enzymes and the malondialdehyde (MDA) content in zebrafish liver and brain were tested after 15 and 30 days beta-CYP enantiomers and racemate exposure under environmentally relevant dosages (0.01 and 0.1 μg/L). According to the acute toxicity results, the 1R-cis-αS and 1R-trans-αS enantiomers were more lethal than 1S-cis-αR and 1S-trans-αR. At 0.1 μg/L, the 1R-cis-αS and 1R-trans-αS enantiomers, and the beta-CYP racemate could significantly induce a hepatic MDA content at 30 days post exposure (dpe), while only 1R-cis-αS caused brain lipid peroxidation. An apparent regulation of antioxidase levels was observed in zebrafish liver and brain after exposure to the 1R-cis-αS and 1R-trans-αS enantiomers, and the beta-CYP racemate. In contrast, no significant oxidative stress was observed in zebrafish exposed to 1S-cis-αR and 1S-trans-αR enantiomers under the test concentrations. This work demonstrated the occurrence of enantioselectivity in toxicity and oxidative stress of beta-CYP to adult zebrafish, which should be considered in environmental risk assessments.

Chiral Derivatives of Xanthones: Investigation of the Effect of Enantioselectivity on Inhibition of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

Searching of new enantiomerically pure chiral derivatives of xanthones (CDXs) with potential pharmacological properties, particularly those with anti-inflammatory activity, has remained an area of interest of our group. Herein, we describe in silico studies and in vitro inhibitory assays of cyclooxygenases (COX-1 and COX-2) for different enantiomeric pairs of CDXs. The evaluation of the inhibitory activities was performed by using the COX Inhibitor Screening Assay Kit. Docking simulations between the small molecules (CDXs; known ligands and decoys) and the enzyme targets were undertaken with AutoDock Vina embedded in PyRx—Virtual Screening Tool software. All the CDXs evaluated exhibited COX-1 and COX-2 inhibition potential as predicted. Considering that the (S)-(−)-enantiomer of the nonsteroidal anti-inflammatory drug ketoprofen preferentially binds to albumin, resulting in lower free plasma concentration than (R)-(+)-enantiomer, protein binding affinity for CDXs was also evaluated by spectrofluorimetry as well as in in silico. For some CDXs enantioselectivity was observed.