RESUMO
The aim of this study was to evaluate the sensitivity of the prawn Palaemon argentinus to the pyrethroid cypermethrin (CYP) and the tetramic acid spirotetramat (STM). These treatments were compared with prawns collected at a reference site to define their basal physiological state. Initially, physicochemical parameters and several pollutants at the selected site were analyzed. The LC50-96 h was determined in adult prawns. Then, prawns were exposed for 96 h to sublethal concentrations of CYP (0.0005 µg/l) and STM (0.44 mg/l) to evaluate the effects on some biochemical endpoints. A treatment combining both pesticides was also added at 5 % of these values. Controls with and without solvent (acetone) were included. The LC50-96 h values were 0.005 µg/l and 4.43 mg/l for CYP and STM, respectively. Moreover, some biomarkers linked to oxidative and energy metabolism were analyzed in the hepatopancreas and muscle of both essayed prawns and those at the basal state. The STM caused a significant decrease in total protein content (32 %) in contrast to the increase of protein carbonyl content (71 %) (p < 0.05). Also, glutathione S-transferase (52 %) and catalase (61 %) activities in the hepatopancreas of exposed prawns were higher compared to both the control and state basal groups (p < 0.05). In muscle, only a significant decrease in the lactate content (69 %) was caused by STM (p < 0.05). In addition, CYP caused a significant increase in the lactate dehydrogenase activity (110 %) in muscle and triacylglycerol content (73 %) in the hepatopancreas (p < 0.05). The integrated biomarker index (IBRv2) analysis showed that STM caused greater damage than CYP. Besides, the combined treatment showed an antagonistic interaction between both insecticides. The differential response of biomarkers to both CYP and STM exposure with respect to their basal levels shows a high sensitivity of P. argentinus demonstrating its potential role as a bioindicator organism.
Assuntos
Biomarcadores , Inseticidas , Palaemonidae , Piretrinas , Compostos de Espiro , Poluentes Químicos da Água , Animais , Palaemonidae/efeitos dos fármacos , Inseticidas/toxicidade , Piretrinas/toxicidade , Compostos de Espiro/toxicidade , Poluentes Químicos da Água/toxicidade , Biomarcadores/metabolismo , Compostos Aza/toxicidade , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/metabolismoRESUMO
BACKGROUND: Compatibility studies of insecticides and natural enemies usually focus on short-term lethal effects, without considering the long-term sublethal effects (including progeny). Even less-explored are the effects of commercial insecticides formulated with more than one active product. Short- and long-term lethal and sublethal effects were studied for the first time on the progeny of commercial formulations of spirotetramat, imidacloprid and a commercial mixture of these active ingredients on pupae of Diaeretiella rapae (M'ntosh) (Hymenoptera: Braconidae), an endoparasitoid of aphids considered to be a potential biological control agent. Insecticides were exposed topically on aphid mummies in which the parasitoid was in the pupal stage. RESULTS: Imidacloprid reduced adult emergence by more than 30% and prolonged intra-host development time with respect to control from half the maximum recommended field dose (MFRD). Spirotetramat and commercial mixture only showed significant effects on these endpoints at doses above the MFRD. The tested formulations did not affect adult longevity, sex ratio, and percentage of parasitism in the exposed generation. At low concentrations the active ingredients in the commercial mixture behave synergistically, whereas at medium and high concentrations they behave antagonistically. Considering the 10% lethal dose (LD10), imidacloprid showed the highest hazard coefficient, whereas the commercial mixture was more hazardous when considering the LD50 and LD90. The commercial mixture and imidacloprid induced higher adult emergence and altered the sex ratio in the progeny. CONCLUSIONS: The following order of toxicity on D. rapae can be established: imidacloprid > commercial mixture > spirotetramat. Joint use of this species with imidacloprid and commercial mixture should be avoided in integrated pest management programs. © 2024 Society of Chemical Industry.
Assuntos
Compostos Aza , Inseticidas , Neonicotinoides , Nitrocompostos , Pupa , Compostos de Espiro , Vespas , Animais , Compostos de Espiro/toxicidade , Pupa/efeitos dos fármacos , Pupa/crescimento & desenvolvimento , Vespas/efeitos dos fármacos , Vespas/fisiologia , Vespas/crescimento & desenvolvimento , Afídeos/efeitos dos fármacos , Afídeos/parasitologia , Feminino , Imidazóis/toxicidadeRESUMO
Imatinib mesylate was the first representative BCR-ABL1 tyrosine kinase inhibitor (TKI) class for the treatment of chronic myeloid leukemia. Despite the revolution promoted by TKIs in the treatment of this pathology, a resistance mechanism occurs against all BCR-ABL1 inhibitors, necessitating a constant search for new therapeutic options. To develop new antimyeloproliferative substances, we applied a medicinal chemistry tool known as molecular hybridization to design 25 new substances. These compounds were synthesized and biologically evaluated against K562 cells, which express BCR-ABL1, a constitutively active tyrosine kinase enzyme, as well as in WSS-1 cells (healthy cells). The new compounds are conjugated hybrids that contain phenylamino-pyrimidine-pyridine (PAPP) and an isatin backbone, which are the main pharmacophoric fragments of imatinib and sunitinib, respectively. A spiro-oxindole nucleus was used as a linker because it occurs in many compounds with antimyeloproliferative activity. Compounds 2a, 2b, 3c, 4c, and 4e showed promise, as they inhibited cell viability by between 45% and 61% at a concentration of 10 µM. The CC50 of the most active substances was determined to be within 0.8-9.8 µM.
Assuntos
Antineoplásicos , Sobrevivência Celular , Mesilato de Imatinib , Oxindóis , Humanos , Células K562 , Mesilato de Imatinib/farmacologia , Oxindóis/farmacologia , Oxindóis/síntese química , Oxindóis/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Relação Estrutura-Atividade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Relação Dose-Resposta a Droga , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/metabolismo , Compostos de Espiro/farmacologia , Compostos de Espiro/química , Compostos de Espiro/síntese química , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Biofilms are a bacterial resistance strategy through which microorganisms organize themselves in the form of a colony fixed to a surface that is protected by a polymer matrix. Infectious diseases that result in biofilm formation have been considered a relevant public health problem due to the potential to increase patient morbidity and mortality, in addition to increasing the burden on health services. Such pathologies are treated with the use of antimicrobial drugs, the indiscriminate use of which has contributed to the process of bacterial resistance, demanding the need to invest in new alternatives to combat them. Based on this, the present work aimed to evaluate the anti-biofilm formation and eradication capacity of Hecogenin Acetate, a steroidal sapogenin of natural origin with important antibacterial properties. For this, we used strains of Streptococcus mutans INCQS 00,446 (ATCC 25,175), Enterococcus faecalis INCQS 00,018 (ATCC 14,506), Staphylococcus epidermidis INCQS 00,016 (ATCC 12,228), Staphylococcus aureus ATCC 25,923, Pseudomonas aeruginosa ATCC 9027 and Escherichia coli ATCC 259,223. The formation, formation inhibition and treatment assays were carried out in microdilution plates and revealed using the crystal violet method. Readings were carried out using absorbance at wavelengths of 492 nm. All tests were performed in triplicate and statistical analyzes were performed using Graphpad Prism v.5.0 software. It was observed that the bacterial strains used have a relevant capacity for biofilm formation, with the Gram positive ones identified in the present study as the best former. In the results of the analyzes with bacterial biofilm, it was identified that Hecogenin Acetate had a relevant antibiofilm capacity, and could therefore serve as a basis for further research into the development of new antimicrobial drugs.
Assuntos
Anti-Infecciosos , Compostos de Espiro , Esteroides , Humanos , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Bactérias , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
Reduced-risk insecticides and mirid predators have been used to control Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) in tomato crops. However, even when causing low mortality to the beneficial insects, these products might cause side effects. This study investigated the sublethal and transgenerational effects of buprofezin, cyantraniliprole, and spiromesifen on Macrolophus basicornis (Stal) (Hemiptera: Miridae). After 72 h of exposure of third-instar nymphs and adults to residues on tomato leaves, adult couples were formed and kept in cages with residue-free tomato leaves. The leaves were changed every 48 h and the offspring were assessed in 6 different periods. Body size was assessed by measuring the hind-tibia length of adults (F0) from exposed nymphs and in three different offspring groups. None of the insecticide residues caused a reduction on offspring populations or affected the body size of adults in generation F0. Regardless, buprofezin and spiromesifen reduced the tibia length of adults (F1) from exposed nymphs assayed in the third mating period. Cyantraniliprole did not affect any parameter and could be recommended for control of B. tabaci in association with M. basicornis releases. This study may contribute to future field assays of the compatibility of these insecticides with M. basicornis.
Assuntos
Hemípteros , Heterópteros , Inseticidas , Pirazóis , Solanum lycopersicum , Compostos de Espiro , Tiadiazinas , ortoaminobenzoatos , Animais , Inseticidas/farmacologia , NinfaRESUMO
RATIONALE: Recently, we demonstrated that the activation of the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) signaling facilitates depressive-like behaviors. Additionally, literature findings support the ability of the N/OFQ-NOP system to modulate the hypothalamic-pituitary-adrenal (HPA) axis. OBJECTIVES: Considering that dysfunctional HPA axis is strictly related to stress-induced psychopathologies, we aimed to study the role of the HPA axis in the pro-depressant effects of NOP agonists. METHODS: Mice were treated prior to stress with the NOP agonist Ro 65-6570, and immobility time in the forced swimming task and corticosterone levels were measured. Additionally, the role of endogenous glucocorticoids and CRF was investigated using the glucocorticoid receptor antagonist mifepristone and the CRF1 antagonist antalarmin in the mediation of the effects of Ro 65-6570. RESULTS: The NOP agonist in a dose-dependent manner further increased the immobility of mice in the second swimming session compared to vehicle. By contrast, under the same conditions, the administration of the NOP antagonist SB-612111 before stress reduced immobility, while the antidepressant nortriptyline was inactive. Concerning in-serum corticosterone in mice treated with vehicle, nortriptyline, or SB-612111, a significant decrease was observed after re-exposition to stress, but no differences were detected in Ro 65-6570-treated mice. Administration of mifepristone or antalarmin blocked the Ro 65-6570-induced increase in the immobility time in the second swimming session. CONCLUSIONS: Present findings suggest that NOP agonists increase vulnerability to depression by hyperactivating the HPA axis and then increasing stress circulating hormones and CRF1 receptor signaling.
Assuntos
Cicloeptanos , Imidazóis , Peptídeos Opioides , Piperidinas , Receptores Opioides , Compostos de Espiro , Camundongos , Animais , Receptores Opioides/fisiologia , Peptídeos Opioides/metabolismo , Glucocorticoides/farmacologia , Nortriptilina/farmacologia , Receptor de Nociceptina , Corticosterona/farmacologia , Sistema Hipotálamo-Hipofisário/metabolismo , Mifepristona/farmacologia , Sistema Hipófise-Suprarrenal/metabolismoRESUMO
Two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is a phytophagous haplodiploid mite and its control is largely based on the use of pesticides. But, the short life cycle and high reproductive rate allow them to develop resistance to many pesticides. To design a strategy for resistance management, a fitness cost study was conducted on different populations of T. urticae, i.e., spiromesifen selected (SPIRO-SEL), unselected (Unsel), and reciprocal crosses. After twelve rounds of selections, T. urticae developed high spiromesifen resistance (71.7-fold) compared to the Unsel strain. Results showed a fitness cost for SPIRO-SEL, Cross1 (Unsel â × SPIRO-SEL â), and Cross2 (SPIRO-SEL â × Unsel â) with a relative fitness values of 0.63, 0.86, and 0.70, respectively. There was a significant increase in the incubation period, quiescent larvae, and egg to adult male and female developmental period of the SPIRO-SEL compared with Unsel strain. Moreover, resistance to spiromesifen was unstable with a decline in resistance value of - 0.05. The presence of unstable spiromesifen resistance associated with fitness costs suggests that intermittent withdrawal of its usage could potentially preserve its effectiveness for management of T. urticae.
Assuntos
Acaricidas , Praguicidas , Compostos de Espiro , Tetranychidae , Feminino , Masculino , AnimaisRESUMO
In this work a microwave-assisted Knoevenagel/Michael/cyclization multicomponent domino methodology, using ethanol as solvent and the ionic liquid 1-methylimidazolium chloride as catalyst was developed for the synthesis of spiro compounds. The reaction conditions considered ideal were determined from a methodological study varying solvent, catalyst, amount of catalyst, temperature, and heating mode. Finally, the generality of the methodology was evaluated by exploring the scope of the reaction, varying the starting materials (isatin, malononitrile, and barbituric acid). Overall, the twelve spiro compounds were synthesized in good yields (43-98%) and the X-ray structure of compound 1b was obtained. In addition, the in vitro antiproliferative activities of the spirocycles against four types of human cancer cell lines including HCT116 (human colon carcinoma), PC3 (prostate carcinoma), HL60 (promyelocytic leukemia), and SNB19 (astrocytoma) were screened by MTT-based assay. It is noteworthy that spiro compound 1c inhibited the four cell lines tested with the lowest IC50 values: 52.81 µM for HCT116, 74.40 µM for PC3, 101 µM for SNB19, and 49.72 µM for HL60.
Assuntos
Carcinoma , Líquidos Iônicos , Compostos de Espiro , Humanos , Compostos de Espiro/farmacologia , Compostos de Espiro/química , Ciclização , Micro-Ondas , SolventesRESUMO
BACKGROUND: Acridine compounds have been described as promising anticancer agents. Previous studies showed that (E)-1'-((4-chlorobenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-06), a spiro-acridine compound, has antitumor activity on Ehrlich tumor and low toxicity. Herein, we investigated its antitumor effect against human cells in vitro. METHODS: MTT assay was used to assess cytotoxicity of AMTAC-06 (3.125-200 µM) against tumor and non-tumor cells, and the half-maximal inhibitory concentration (IC50) and the selectivity index (SI) were calculated. The effects on the cell cycle (propidium iodide-PI-staining), apoptosis (Annexin V-FITC/PI double staining by flow cytometry), and production of reactive oxygen species, ROS (DCFH assay) were also evaluated. Statistical analysis was achieved using ANOVA followed by Tukey's post-test. RESULTS: AMTAC-06 showed higher cytotoxicity against colorectal carcinoma HCT-116 cells (IC50: 12.62 µM). The SI showed that AMTAC-06 was more selective for HCT-116 cells (HaCaT SI: 1.41; PBMC SI: 0.62) than doxorubicin (HaCaT SI: 0.10; PBMC SI: 0.01). AMTAC-06 (15 and 30 µM) induced an increase in the sub-G1 peak (p < 0.000001) and cell cycle arrest in S phase (p = 0.003547). Moreover, treatment with this compound (15 and 30 µM) resulted in increased early (p < 0.000001) and late apoptotic cells (p < 0.000001). In addition, there was a reduction on ROS production (p < 0.000001). CONCLUSIONS: AMTAC-06 presents anticancer activity against HCT-116 cells by regulating the cell cycle, inducing apoptosis and an antioxidant action.
Assuntos
Antineoplásicos , Neoplasias Colorretais , Compostos de Espiro , Acridinas/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Células HCT116 , Humanos , Leucócitos Mononucleares/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Compostos de Espiro/farmacologiaRESUMO
We report herein an alternative method for the synthesis of seleno-dibenzocycloheptenones and seleno-spiro[5.5]trienones through the radical cyclization of biaryl ynones in the presence of diorganyl diselenides, using Oxone as a green oxidizing agent. The reactions were conducted using acetonitrile as the solvent in a sealed tube at 100 °C. The protocol is operationally simple and scalable, exhibits high regioselectivity, and allows the synthesis of 24 dibenzocycloheptenones/spiro[5.5]trienones in yields of up to 99%, 17 of which are unpublished compounds. Additionally, synthetic transformations of the prepared compounds, such as oxidation and reduction reactions, are demonstrated.