RESUMO
Aim: Our study evaluated the activity of sertraline (SER) alone and associated with antifungal drugs in planktonic Candida spp. strains, and investigated its mechanism of action. Materials & methods: Broth microdilution method and minimum fungicidal concentration/MIC ratio were used to assess SER anticandidal activity, and the interaction with antifungals was determined by fractional inhibitory concentration index. The mechanism of action was investigated by flow cytometry and in silico tests. Results: SER inhibited Candida spp. strains at low concentrations by the fungicidal effect and showed no loss of effectiveness when combined. Its action seemed to be related to the membrane and cell wall biosynthesis inhibition. Conclusion: SER has activity against Candida spp. isolated and associated with antifungals, and acts by causing cell wall and membrane damage.
Assuntos
Antifúngicos , Candida , Antifúngicos/farmacologia , Sertralina/farmacologia , Parede Celular , Testes de Sensibilidade MicrobianaRESUMO
Objective: To evaluate the antifungal activity of hydralazine hydrochloride alone and in synergy with azoles against Candida spp. and the action mechanism. Methods: We used broth microdilution assays to determine the MIC, checkerboard assays to investigate synergism, and flow cytometry and molecular docking tests to ascertain action mechanism. Results: Hydralazine alone had antifungal activity in the range of 16-128 µg/ml and synergistic effect with itraconazole versus 100% of the fungal isolates, while there was synergy with fluconazole against 11.11% of the isolates. There was molecular interaction with the receptors exo-B(1,3)-glucanase and CYP51, causing reduced cell viability and DNA damage. Conclusion: Hydralazine is synergistic with itraconazole and triggers cell death of Candida spp. at low concentrations, demonstrating antifungal potential.
Assuntos
Antifúngicos , Triazóis , Antifúngicos/farmacologia , Triazóis/farmacologia , Candida , Itraconazol/farmacologia , Plâncton , Simulação de Acoplamento Molecular , Fluconazol/farmacologia , Hidralazina/farmacologia , Testes de Sensibilidade Microbiana , Farmacorresistência FúngicaRESUMO
Aim: To evaluate the antibacterial activity of paroxetine alone and associated with oxacillin against isolates of methicillin-sensitive and -resistant Staphylococcus aureus. Materials & methods: The broth microdilution and checkerboard techniques were used, with investigation of possible mechanisms of action through flow cytometry, fluorescence microscopy and molecular docking, in addition to scanning electron microscopy for morphological analysis. Results: Paroxetine showed a MIC of 64 µg/ml and bactericidal activity, mostly additive interactions in combination with oxacillin, evidence of action on genetic material and membrane, morphological changes in microbial cells and influence on virulence factors. Conclusion: Paroxetine has antibacterial potential from the perspective of drug repositioning.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Paroxetina/farmacologia , Simulação de Acoplamento Molecular , Antibacterianos/farmacologia , Oxacilina/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Testes de Sensibilidade MicrobianaRESUMO
Objective: The present study investigated the antifungal action of dexamethasone disodium phosphate (Dex). Methodology: Susceptibility testing was performed using the Clinical & Laboratory Standards Institute protocol; M27-A3, checkerboard test and biofilm were evaluated with two isolates of Candida albicans, hyphal production test, molecular docking analysis and flow cytometry analysis. Result: Dex and fluconazole (FLC) together had a synergistic effect. Mature biofilm was reduced when treated with Dex alone or in combination. Dex and FLC promoted a decrease in the production of hyphae and changes in the level of mitochondrial depolarization, increased generation of reactive oxygen species, loss of membrane integrity, increased phosphatidylserine externalization and molecular docking; there was interaction with ALS3 and SAP5 targets. Conclusion: Dex showed antifungal activity against FLC-resistant C. albicans strains.
This study aimed to evaluate the antifungal action of dexamethasone against FLC-resistant C. albicans strains.
Assuntos
Candida albicans , Fluconazol , Antifúngicos/farmacologia , Biofilmes , Dexametasona/farmacologia , Farmacorresistência Fúngica , Sinergismo Farmacológico , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento MolecularRESUMO
Aim: To evaluate the antifungal activity of gallic acid (GA) against the strains of Candida spp. resistant to fluconazole and to determine its mechanism of action. Materials & methods: Antifungal activity was evaluated using the broth microdilution and flow cytometry techniques. Results: GA presented minimum inhibitory concentrations ranging from 16 to 72 µg/ml, causing alterations of the membrane integrity and mitochondrial transmembrane potential, production of reactive oxygen species and externalization of phosphatidylserine. Conclusion: GA has potential antifungal activity against Candida spp.
Assuntos
Antifúngicos , Candida albicans , Antifúngicos/farmacologia , Apoptose , Morte Celular , Farmacorresistência Fúngica , Fluconazol/farmacologia , Ácido Gálico/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Aim: To evaluate the activity of diclofenac sodium and synergism with oxacillin against clinical strains of SARM in plactonic cells, antibiofilm and biofilm. Materials & methods: Synergism activity was assessed using the fractional inhibitory concentration index and its possible mechanism of action by flow cytometry. Results: The synergistic activity of diclofenac sodium with oxacillin was observed against plactonic cells, antibiofilm and in biofilm formed from clinical methicillin-resistant Staphylococcus aureus strains. Conclusion: This combination caused damage to the integrity of the membrane and ruptures in the DNA of the cells, leading to apoptosis.
Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Diclofenaco/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Oxacilina/farmacologia , Biofilmes/crescimento & desenvolvimento , Membrana Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Sinergismo Farmacológico , Testes de Sensibilidade MicrobianaRESUMO
Aim: The purpose of this study was to evaluate the antifungal activity of midazolam, alone and in association with azoles, against isolates of clinical Candida spp. in planktonic and biofilm form. Materials & methods: The antifungal activity was observed using the broth microdilution technique. Flow cytometry tests were performed to investigate the probable mechanism of action and the comet test and cytotoxicity test were applied to evaluate DNA damage. Results: Midazolam (MIDAZ) showed antifungal activity against planktonic cells (125-250 µg/ml) and reduced the viability of Candida spp. biofilms (125 a 2500 µg/ml). The interaction of MIDAZ against Candida spp. biofilms was observed through scanning electron microscopy, causing alteration of their appearance. Therefore, MIDAZ has antifungal potential against Candida spp.
Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candidíase/microbiologia , Midazolam/farmacologia , Biofilmes/efeitos dos fármacos , Candida/genética , Candida/crescimento & desenvolvimento , Candida/fisiologia , Avaliação Pré-Clínica de Medicamentos , Farmacorresistência Fúngica , Fluconazol/farmacologia , Humanos , Testes de Sensibilidade MicrobianaRESUMO
Aim: The purpose of this study was to assess the antifungal effect of ß-lapachone (ß-lap) on azole-resistant strains of Candida spp. in both planktonic and biofilm form. Materials & methods: The antifungal activity of ß-lap was evaluated by broth microdilution, flow cytometry and the comet assay. The cell viability of the biofilms was assessed using the MTT assay. Results: ß-lap showed antifungal activity against resistant strains of Candida spp. in planktonic form. In addition, ß-lap decreased the viability of mature biofilms and inhibited the formation of biofilms in vitro. Conclusion: ß-lap showed antifungal activity against Candida spp., suggesting that the compound can be utilized as an adjunct agent in the treatment of candidiasis.
Assuntos
Antifúngicos/farmacologia , Azóis/farmacologia , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Farmacorresistência Fúngica , Naftoquinonas/farmacologia , Candida/fisiologia , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Humanos , Testes de Sensibilidade MicrobianaRESUMO
Aim: The purpose of this study was to evaluate the antimicrobial activity of the anesthetic etomidate against strains of MRSA and biofilms. Materials & methods: The antibacterial effect of etomidate was assessed by the broth microdilution method. To investigate the probable action mechanism of the compound flow cytometry techniques were used. Results: MRSA strains showed MIC equal to 500 and 1000 µg/ml of etomidate. Four-fifths (80%) of the tested MRSA strains demonstrated synergistic effect with oxacillin. Etomidate also showed activity against MRSA biofilm at concentration of 250 µg/ml. Cytometric analysis revealed that the cells treated with etomidate leading to cell death, probably by apoptosis. Conclusion: Etomidate showed antibacterial activity against MRSA.
Assuntos
Antibacterianos/farmacologia , Etomidato/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Oxacilina/farmacologia , Biofilmes/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologiaRESUMO
Synthetically derived samples of (+)-(6aS,11aS)-2,3,9-trimethoxypterocarpan [(+)-1] and its enantiomer [(-)-1], both of which are examples of naturally occurring isoflavonoids, were evaluated, together with the corresponding racemate, as cytotoxic agents against the HL-60, HCT-116, OVCAR-8, and SF-295 tumor cell lines. As a result it was established that compound (+)-1 was particularly active with OVCAR-8 cells being the most sensitive and responding in a dose-dependent manner. A study of cell viability and drug-induced morphological changes revealed the compound causes cell death through a mechanism characteristic of apoptosis. Finally, a computational study of the interactions of compound (+)-1 and (S)-monastrol, an established, synthetically derived, potent, and cell-permeant inhibitor of mitosis, with the kinesin-type protein Eg5 revealed that both bind to this receptor in a similar manner. Significantly, compound (+)-1 binds with greater affinity, an effect attributed to the presence of the associated methoxy groups.
RESUMO
Aim: The purpose of this study was to evaluate the effect of etomidate alone and in combination with azoles on resistant strains of Candida spp. in both planktonic cells and biofilms. Materials & methods: The antifungal activity of etomidate was assessed by the broth microdilution test; flow cytometric procedures to measure fungal viability, mitochondrial transmembrane potential, free radical generation and cell death; as well detection of DNA damage using the comet assay. The interaction between etomidate and antifungal drugs (itraconazole and fluconazole) was evaluated by the checkerboard assay. Results: Etomidate showed antifungal activity against resistant strains of Candida spp. in planktonic cells and biofilms. Etomidate also presented synergism with fluconazole and itraconazole in planktonic cells and biofilms. Conclusion: Etomidate showed antifungal activity against Candida spp., indicating that it is a possible therapeutic alternative.
Assuntos
Antifúngicos/farmacologia , Azóis/farmacologia , Candida/efeitos dos fármacos , Farmacorresistência Fúngica , Etomidato/farmacologia , Fluconazol/farmacologia , Animais , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Dano ao DNA/efeitos dos fármacos , Descoberta de Drogas , Sinergismo Farmacológico , Fibroblastos/efeitos dos fármacos , Pulmão/citologia , Pulmão/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Testes de Sensibilidade MicrobianaRESUMO
The cytotoxic activity of the pimarane diterpene annonalide (1) and nine of its semisynthetic derivatives (2-10) was investigated against the human tumor cell lines HL-60 (leukemia), PC-3 (prostate adenocarcinoma), HepG2 (hepatocellular carcinoma), SF-295 (glioblastoma) and HCT-116 (colon cancer), and normal mouse fibroblast (L929) cells. The preparation of 2-10 involved derivatization of the side chain of 1 at C-13. Except for 2, all derivatives are being reported for the first time. Most of the tested compounds presented IC50s below 4.0⯵M, being considered potential antitumor agents. The structures of all new compounds were elucidated by spectroscopic analyses including 2D NMR and HRMS. Additionally, the interaction of annonalide (1) with ctDNA was evaluated using spectroscopic techniques, and the formation of a supramolecular complex with the macromolecule was confirmed. Competition assays with fluorescent probes (Hoechst and ethidium bromide) and theoretical studies confirmed that 1 interacts preferentially via DNA intercalation with stoichiometric ratio of 1:1 (1:ctDNA). The ΔG value was calculated as -28.24â¯kJâ¯mol-1, and indicated that the interaction process occurs spontaneously. Docking studies revealed that van der Walls is the most important interaction in 1-DNA and EB-DNA complexes, and that both ligands (1 and EB) interact with the same DNA residues (DA6, DA17 and DT19).
Assuntos
Ciclo-Octanos/química , DNA/química , Cetonas/química , Animais , Sítios de Ligação , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular , Ciclo-Octanos/síntese química , Ciclo-Octanos/toxicidade , DNA/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Cetonas/síntese química , Cetonas/toxicidade , Simulação de Acoplamento Molecular , Conformação de Ácido Nucleico , Espectrofotometria , Eletricidade Estática , Termodinâmica , Temperatura de TransiçãoRESUMO
BACKGROUND: Remirea maritima has been widely used in the treatment of diarrhea, kidney disease, and high fever and for therapeutic purposes, such as an analgesic and anti-inflammatory. However, few scientific research studies on its medicinal properties have been reported. PURPOSE: The present study aimed to investigate the anticancer potential of aqueous extract (AE), 40% hydroalcoholic extracts (40HA) and 70% (70HA) from R. maritima in experimental models and to identify its phytochemical compounds. METHODS: The chemical composition of AE, 40HA and 70HA was assessed by HPLC-DAD and ESI-IT-MS/MS. In vitro activity was determined on cultured tumor cell, NCI-H385N (Broncho-alveolar carcinoma), OVCAR-8 (Ovarian carcinoma) and PC-3M (prostate carcinoma) by the MTT assay, and the in vivo antitumor activity was assessed in Sarcoma 180-bearing mice. Toxicological parameters were also evaluated as well as the humoral immune response. RESULTS: Among the aqueous and hydroalcoholic extracts of R. maritima, only 40HA showed in vitro biological effect potential, presenting IC50 values of 27.08, 46.62 and >50µg/ml for OVCAR-8, NCI-H385M and PC-3M cells lines, respectively. Regarding chemical composition, a mixture of isovitexin-2''-O-ß-D-glucopyranoside, vitexin-2''-O-ß-D-glucopyranoside, luteolin-7-O-glucuronide and 1-O-(E)-caffeoyl-ß-D-glucose were identified as the major phytochemical compounds of the extracts. In the in vivo study, the tumor inhibition rates were 57.16-62.57% at doses of 25mg/kg and 50mg/kg, respectively, and the tumor morphology presented increasing numbers of apoptotic cells. Additionally, 40HA also demonstrated significantly increased of OVA-specific total Ig. CONCLUSIONS: 40HA exhibited in vitro and in vivo anticancer properties without substantial toxicity that could be associated with its immunostimulating properties.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Cyperaceae/química , Extratos Vegetais/efeitos adversos , Extratos Vegetais/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Etanol , Humanos , Imunidade Humoral/efeitos dos fármacos , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Fenóis/química , Fenóis/farmacologia , Solventes , Espectrometria de Massas por Ionização por Electrospray , ÁguaRESUMO
Biflorin 1 is a biologically active quinone, isolated from Capraria biflora. Five new biflorin-based nitrogen derivatives were synthesized, of which two were mixtures of (E)- and (Z)- isomers: (Z)-2a, (Z)-2b, (Z)-3a, (Z)- and (E)-3b, (Z)- and (E)-3c. The antibacterial activity was investigated using the microdilution method for determining the minimum inhibitory concentration (MIC) against six bacterial strains. Tests have shown that these derivatives have potential against all bacterial strains. The cytotoxic activity was also evaluated against three strains of cancer cells, but none of the derivatives showed activity.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Hidrazonas/farmacologia , Naftoquinonas/farmacologia , Oximas/farmacologia , Scrophulariaceae/química , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Linhagem Celular Tumoral , Humanos , Hidrazonas/síntese química , Hidrazonas/química , Testes de Sensibilidade Microbiana , Naftoquinonas/síntese química , Naftoquinonas/química , Neoplasias/tratamento farmacológico , Oximas/síntese química , Oximas/químicaRESUMO
OBJECTIVES: The aim of this study was to investigate the cytotoxic and antitumour effects of the essential oil from the leaves of Mentha x villosa (EOMV) and its main component (rotundifolone). METHODS: In-vitro cytotoxic activity of the EOMV and rotundifolone was determined on cultured tumour cells. In-vivo antitumour activity of the EOMV was assessed in sarcoma 180-bearing mice. KEY FINDINGS: The EOMV displayed cytotoxicity against human tumour cell lines, showing IC50 values in the range of 0.57-1.02 µg/ml in the HCT-116 and SF-295 cell lines, respectively. Rotundifolone showed weak cytotoxicity against HCT-116, SF-295 and OVCAR-8 cell lines (IC50 > 25.00 µg/ml). Tumour growth inhibition rates were 29.4-40.5% and 25.0-45.2% for the EOMV treatment by intraperitoneal (50-100 mg/kg/day) and oral (100-200 mg/kg/day) administration, respectively. The EOMV did not significantly affect body mass and macroscopy of the organs. CONCLUSIONS: The EOMV possesses significant antitumour activity with low systemic toxicity, possibly due to the synergistic action of its minor constituents.
Assuntos
Antineoplásicos/farmacologia , Mentha , Monoterpenos/farmacologia , Óleos Voláteis/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Feminino , Humanos , Camundongos , Folhas de PlantaRESUMO
In recent decades, the incidence of candidemia in tertiary hospitals worldwide has substantially increased. These infections are a major cause of morbidity and mortality; in addition, they prolong hospital stays and raise the costs associated with treatment. Studies have reported a significant increase in infections by non-albicans Candida species, especially C. tropicalis. The number of antifungal drugs on the market is small in comparison to the number of antibacterial agents available. The limited number of treatment options, coupled with the increasing frequency of cross-resistance, makes it necessary to develop new therapeutic strategies. The objective of this study was to evaluate and compare the antifungal activities of three semisynthetic naphthofuranquinone molecules against fluconazole-resistant Candida spp. strains. These results allowed to us to evaluate the antifungal effects of three naphthofuranquinones on fluconazole-resistant C. tropicalis. The toxicity of these compounds was manifested as increased intracellular ROS, which resulted in membrane damage and changes in cell size/granularity, mitochondrial membrane depolarization, and DNA damage (including oxidation and strand breakage). In conclusion, the tested naphthofuranquinones (compounds 1-3) exhibited in vitro cytotoxicity against fluconazole-resistant Candida spp. strains.
Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Fluconazol/farmacologia , Naftoquinonas/farmacologia , Animais , Antifúngicos/síntese química , Antifúngicos/química , Candida/classificação , Candida/genética , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/genética , Candida tropicalis/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , DNA Fúngico/química , DNA Fúngico/genética , DNA Fúngico/metabolismo , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Modelos Químicos , Dados de Sequência Molecular , Estrutura Molecular , Naftoquinonas/síntese química , Naftoquinonas/química , Fosfatidilserinas , RNA Ribossômico 5,8S/genética , Espécies Reativas de Oxigênio/metabolismo , Análise de Sequência de DNARESUMO
Three new azaphilones with an unusual methylene bridge, named mycoleptones A, B, and C (2, 4, and 5), were isolated from cultures of Mycoleptodiscus indicus, a fungus associated with the South American medicinal plant Borreria verticillata. Additionally, four known polyketides, austdiol (1), eugenitin (3), 6-methoxyeugenin (6), and 9-hydroxyeugenin (7), were also isolated. The structural characterization of compounds was carried out by nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, electronic circular dichroism spectroscopy, time-dependent density functional theory calculations, and X-ray crystallography. Compounds 1-9 were weakly active when tested in antileishmanial and cytotoxicity assays.
Assuntos
Benzofuranos/isolamento & purificação , Endófitos/química , Policetídeos/isolamento & purificação , Benzofuranos/química , Benzofuranos/farmacologia , Brasil , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Leishmania/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Policetídeos/química , Policetídeos/farmacologia , Rubiaceae/microbiologiaRESUMO
The aim of this study was to investigate the chemical composition and anticancer effect of the leaf essential oil of Xylopia frutescens in experimental models. The chemical composition of the essential oil was analysed by GC/FID and GC/MS. In vitro cytotoxic activity of the essential oil was determined on cultured tumour cells. In vivo antitumour activity was assessed in Sarcoma 180-bearing mice. The major compounds identified were (E)-caryophyllene (31.48%), bicyclogermacrene (15.13%), germacrene D (9.66%), δ-cadinene (5.44%), viridiflorene (5.09%) and α-copaene (4.35%). In vitro study of the essential oil displayed cytotoxicity on tumour cell lines and showed IC50 values ranging from 24.6 to 40.0 µg/ml for the NCI-H358M and PC-3M cell lines, respectively. In the in vivo antitumour study, tumour growth inhibition rates were 31.0-37.5%. In summary, the essential oil was dominated by sesquiterpene constituents and has some interesting anticancer activity.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias/tratamento farmacológico , Óleos Voláteis/administração & dosagem , Óleos de Plantas/administração & dosagem , Xylopia/química , Animais , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Camundongos , Neoplasias/fisiopatologia , Óleos Voláteis/química , Folhas de Planta/química , Óleos de Plantas/químicaRESUMO
(4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) is a known cytotoxic compound belonging to the phenstatin family. However, the exact mechanism of action of PHT-induced cell death remains to be determined. The aim of this study was to investigate the mechanisms underlying PHT-induced cytotoxicity. We found that PHT displayed potent cytotoxicity in different tumor cell lines, showing IC50 values in the nanomolar range. Cell cycle arrest in G2/M phase along with the augmented metaphase cells was found. Cells treated with PHT also showed typical hallmarks of apoptosis such as cell shrinkage, chromatin condensation, phosphatidylserine exposure, increase of the caspase 3/7 and 8 activation, loss of mitochondrial membrane potential, and internucleosomal DNA fragmentation without affecting membrane integrity. Studies conducted with isolated tubulin and docking models confirmed that PHT binds to the colchicine site and interferes in the polymerization of microtubules. These results demonstrated that PHT inhibits tubulin polymerization, arrests cancer cells in G2/M phase of the cell cycle, and induces their apoptosis, exhibiting promising anticancer therapeutic potential.
Assuntos
Apoptose/efeitos dos fármacos , Benzofenonas/farmacologia , Divisão Celular/efeitos dos fármacos , Fase G2/efeitos dos fármacos , Moduladores de Tubulina , Tubulina (Proteína)/biossíntese , Anexinas/metabolismo , Antimetabólitos , Benzofenonas/síntese química , Bromodesoxiuridina , Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Membrana Celular/fisiologia , Membrana Celular/ultraestrutura , Sobrevivência Celular/efeitos dos fármacos , Corantes , Ensaio Cometa , Fragmentação do DNA/efeitos dos fármacos , Células HL-60 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Modelos Moleculares , Polimerização , Sais de Tetrazólio , TiazóisRESUMO
CONTEXT: Liver transplantation is one of the last viable resources for patients with end-stage liver disease. Many strategies are been used to improve the number of available organs and overcome waiting list delay. However, hepatic steatosis is one of the mainly concerns when organs are consider to transplantation due to it is importance as a risk factor for primary dysfunction. Surgeons play an important role to decide each organ will be accept or decline and its righteous allocation. OBJECTIVE: Retrospectively evaluate the surgeon assessment of steatosis degree and its confrontation with further histopathologic findings. METHODS: We analyzed 117 patients underwent deceased liver transplantation for end-stage liver disease in University Hospital Walter Cantideo, Fortaleza, CE, Brazil. A matrix table was organized to estimate the categorical data observed. We clustered the subjects into mild (0%-30%) and moderate (30%-60%) steatosis degree under the clinical criteria of organ suitability for transplantation. We categorized the organs as suitable organ for transplant and as non-suitable organ for transplant. Evaluations between the two first assessments, before perfusion (pre-perfusion) vs biopsy findings and after perfusion vs biopsy findings observations were analyzed and also a comparison between pre-perfusion and after perfusion data was performed. RESULTS: On the first assessment, we obtained a 93% of agreement (n = 109) between the two evaluations. On the second assessment, we had an 8% (n = 9) of mistaken allocation. Comparing the observation before (pre-perfusion) and after (after perfusion), we obtained a strong agreement between the surgeons. CONCLUSIONS: Although our experienced surgeon team, we have wrongly evaluated feasible organs for transplantation. Nonetheless, our faulty percentage is low comparing to worldwide percentage.