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1.
Orthop Surg ; 16(3): 559-567, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38214016

RESUMO

OBJECTIVE: Cable-dragged reduction and cantilever beam internal fixation can provide promising results in the treatment of atlantoaxial dislocation or instability. However, bilateral atlantoaxial joints bone autografting has not been conducted in this technique. We aim to evaluate the safety and effectiveness of bilateral atlantoaxial joints bone autografting in posterior cable-dragged reduction and cantilever-beam internal fixation. METHODS: In this retrospective study, we included 14 patients with a minimum 24-month follow-up from December 2019 to September 2020. The granular bone harvested from the iliac crest was packed into the bilateral atlantoaxial joints of 14 patients in posterior cable-dragged reduction and cantilever-beam internal fixation. X-ray imaging and cervical computed tomography (CT) were performed during follow-up. The time required for bone fusion was recorded. The clinical outcomes were evaluated using the JOA scores, NDI, and VAS scores. Mann-Whitney U test, the chi-squared test, or the Fisher exact test were used to compare the two groups regarding patient characteristics, clinical outcomes, bone fusion rates, and cervical sagittal alignment. RESULTS: The operations were successfully performed in all patients without any intraoperative complications. The mean operation time was (169.64 ± 20.91) minutes, and the intraoperative blood loss was (130.71 ± 33.62) mL. All patients received satisfactory reductions and firm bony fusion at the final follow-up. The fusion rates were 64.29% in the atlantoaxial joints and 21.43% in post bone graft area at 3 months postoperatively, and a significant difference was observed (p = 0.022). Besides, the cervical sagittal alignment in all patients was well maintained in the last follow-up compared to preoperatively. Importantly, a complete bony fusion in the atlantoaxial joints was observed in all patients. Moreover, the JOA, NDI, and VAS scores had improved significantly at the last follow-up. CONCLUSION: Bone autografting of the bilateral atlantoaxial joints is a safe and effective technique to increase bone fusion rates, shorten bone fusion time, and reduce complication rates when the cable-dragged reduction and cantilever beam internal fixation approach is used. Therefore, it is a cost-effective surgical procedure for treating patients with atlantoaxial dislocation or instability.


Assuntos
Articulação Atlantoaxial , Luxações Articulares , Fusão Vertebral , Traumatismos da Coluna Vertebral , Humanos , Estudos Retrospectivos , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/cirurgia , Transplante Autólogo , Resultado do Tratamento , Luxações Articulares/cirurgia , Fusão Vertebral/métodos
2.
J Sci Food Agric ; 104(6): 3246-3255, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38081762

RESUMO

BACKGROUND: The aim of this research was to evaluate the possibility of lipid concomitant γ-oryzanol reducing oil absorbency of fried foods and the underlying mechanism. Therefore, the influence of γ-oryzanol on moisture and oil content, and distribution and micromorphology of French fries and the viscosity, fatty acid composition and total polar compounds content of rice bran oil (RBO) after frying were studied. RESULTS: Our results showed that the incorporation of low concentration of γ-oryzanol [low addition group (LAG)] (5.754 g/kg) decreased the oil absorbency and porous structure of French fries during frying. Additionally, LAG incorporation inhibited the degradation of linoleic acid, decreased the growth rate of saturated fatty acids, total polar compounds and viscosity of frying oil. CONCLUSIONS: Consequently, it was recommended to incorporate a small amount of γ-oryzanol in frying oil because it could inhibit oil absorption behavior of French fries. © 2023 Society of Chemical Industry.


Assuntos
Culinária , Fenilpropionatos , Culinária/métodos , Ácidos Graxos , Óleo de Farelo de Arroz
3.
Orthop Surg ; 15(11): 2901-2910, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37737031

RESUMO

OBJECTIVE: The long-term results of cervical disc arthroplasty (CDA) for noncontiguous cervical degenerative disc disease (CDDD) are still uncertain. Moreover, it is unclear whether CDA delays or avoids the degeneration of the intermediate segment (IS), leading to controversy in the field. Therefore, this study aimed to investigate the mid- to long-term clinical and radiographic outcomes of CDA in treating noncontiguous CDDD and to explore whether the IS degenerated faster after CDA than other non-surgically treated adjacent segments. METHODS: We retrospectively analyzed patients with noncontiguous CDDD who underwent CDA in our department between January 2008 and July 2018. The patients were divided into the CDA and hybrid surgery (HS) groups, and clinical and radiographic outcomes were evaluated at routine postoperative intervals. Clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA), neck disability index (NDI), and visual analogue scale (VAS), while radiographic outcomes included cervical lordosis (CL), C2-C7 range of motion (ROM), segmental ROM, and disc angle (DA) at the arthroplasty level. Complications were also evaluated.Pre- and postoperative values were compared using paired t-tests or Wilcoxon rank-sum tests. Independent Student t-tests or Mann-Whitney U tests analyzed continuous data between CDA and HS groups, while chi-square or Fisher exact tests assessed categorical data. RESULTS: Sixty-four patients with noncontiguous CDDD, with 31 in the CDA group and 33 in the HS group, were evaluated. The mean follow-up time was over 70 months. The most frequently involved levels were C4/5 and C5/6. Both groups showed significant improvements in JOA, NDI, and VAS values after surgery. Although CL was maintained, the CL in the CDA group was consistently lower than that in the HS group (p < 0.05). There was a significant decrease in C2-C7 ROM (p < 0.05), but at the last follow-up, the C2-C7 ROM in the CDA group was greater than that in the HS group (p < 0.05). At the last follow-up, 44.3% of arthroplasty levels had developed heterotopic ossification (HO), and 48.45% had developed anterior bone loss (ABL). In addition, adjacent segment degeneration (ASDeg) was observed in the IS (22.7%), superior adjacent segment (20.6%)and inferior adjacent segment (21.9%). CONCLUSION: CDA or CDA combined with fusion are viable treatments for noncontiguous CDDD, with satisfactory outcomes after mid-to-long-term follow-up. ASDeg is similar in non-surgical segments after 70 months of follow-up. ROM of the IS issimilar to preoperative levels, indicating CDA does not increase the risk of IS degeneration.


Assuntos
Degeneração do Disco Intervertebral , Lordose , Fusão Vertebral , Substituição Total de Disco , Humanos , Degeneração do Disco Intervertebral/cirurgia , Seguimentos , Estudos Retrospectivos , Resultado do Tratamento , Artroplastia/métodos , Vértebras Cervicais/cirurgia , Amplitude de Movimento Articular , Lordose/cirurgia , Fusão Vertebral/métodos
4.
BMC Musculoskelet Disord ; 23(1): 641, 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35791024

RESUMO

PURPOSE: To investigate the relationship between the preoperative paraspinal Goutalier grade of fatty infiltration and postoperative cervical sagittal alignment in patients undergoing anterior cervical discectomy and fusion (ACDF). METHODS: A total of 101 patients who underwent single-level ACDF with the Zero-profile implant system between March 2011 and April 2020 were included in this study. Cervical sagittal alignment parameters, including the C2-C7 Cobb angle, functional spinal unit (FSU) angle, cervical sagittal vertical axis (SVA), and T1 slope (T1S), were assessed. Preoperative magnetic resonance images were used to classify patients according to Goutalier grade. Clinical outcomes including Neck Disability Index (NDI) scores, Japanese Orthepaedic Association (JOA) scores and Visual Analogue Scale (VAS) scores were collected and analyzed. RESULTS: According to the Goutalier grade, 33 patients were classified as Goutalier 0-1 (Group A), 44 were classified as Goutalier 1.5-2 (Group B), and 24 were classified as Goutalier 2.5-4.0 (Group C). The mean age among the three groups showed significant differences (P = 0.007). At the last follow-up, the C2-C7 Cobb angle, FSU angle, and T1S improved after the surgery among the groups. Although there were varying degrees of loss of curvature among the different groups during the follow-up period, the postoperative cervical sagittal alignment parameters demonstrated no statistical differences among the three groups (P > 0.05). In addition, patients in all groups experienced significant relief of their symptoms, and the clinical scores were comparable among the groups (P > 0.05). CONCLUSION: The complex nature of anterior cervical surgery requires surgical attention both in decompression and sagittal alignment. Our study demonstrates satisfactory postoperative cervical sagittal alignment of patients despite different grades of fatty infiltration of the multifidus muscle following single-level ACDF. Based on our results, the improvement and maintenance of cervical sagittal alignment after ACDF remains a complex problem that spine surgeons should consider before surgery.


Assuntos
Vértebras Cervicais , Fusão Vertebral , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Discotomia/métodos , Humanos , Músculos/cirurgia , Pescoço , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos
5.
J Orthop Surg Res ; 16(1): 518, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34416892

RESUMO

BACKGROUND: The surgical outcomes of anterior cervical discectomy and fusion (ACDF) in female patients according to menopausal status remain unclear. The objective of this study was to investigate the differences in these outcomes among female patients with different menopausal statuses. METHODS: Ninety-one patients undergoing single-level or consecutive two-level ACDF with a minimum 12-month postoperative follow-up were included in this study. There were 38 patients in the premenopausal group, 28 patients in the early postmenopausal group, and 25 patients in the late postmenopausal group. The clinical outcomes were evaluated by means of the neck disability index (NDI) scores, Japanese Orthopedic Association (JOA) scores, and visual analog scale (VAS) scores. Radiological parameters included cervical lordosis (CL), the functional spinal unit (FSU) angle, range of motion (ROM) of the total cervical spine, ROM of the FSU, anterior and posterior FSU height, implant subsidence, adjacent segment degeneration (ASD), and Hounsfield unit (HU) values. RESULTS: All groups showed significant improvements in their JOA, VAS, and NDI scores (P < 0.05). The differences in preoperative and final follow-up CL, ROM of C2-7, FSU angle, and ROM of FSU were not statistically significant among the three groups (P > 0.05). The anterior FSU height loss rate showed a significant difference (P = 0.043), while there was no difference in the posterior FSU height loss rate (P = 0.072). The fusion rates in the early and late postmenopausal groups were consistently lower than those in the premenopausal group during the follow-up period. All patients had satisfactory outcomes at the final follow-up. CONCLUSION: There were no significant differences in clinical or other related outcomes of single-level or consecutive two-level ACDF in the long term among female patients with different menopausal statuses. However, the early bony fusion rates and anterior FSU height loss rates were poorer in late postmenopausal patients than in premenopausal or early postmenopausal patients. Hence, importance should be attached to the protection of late postmenopausal patients in the early postoperative period to guarantee solid bony fusion.


Assuntos
Degeneração do Disco Intervertebral , Lordose , Fusão Vertebral , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Discotomia/efeitos adversos , Feminino , Seguimentos , Humanos , Degeneração do Disco Intervertebral/cirurgia , Menopausa , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do Tratamento
7.
BMC Musculoskelet Disord ; 21(1): 457, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660463

RESUMO

BACKGROUND: Cervical disc arthroplasty (CDA) has been demonstrated, in clinical trials, as an effective and safe treatment for patients diagnosed with radiculopathy and/or myelopathy. However, the current CDA indication criteria, based on the preoperative segmental range of motion (ROM), comprises a wide range of variability. Although the arthroplasty level preserved ROM averages 7°-9° after CDA, there are no clear guidelines on preoperatively limited or excessive ROM at the index level, which could be considered as suitable for CDA. METHODS: This was a retrospective study of patients who underwent CDA between January 2008 and October 2018 using Prestige-LP discs in our hospital. They were divided into the small-ROM (≤5.5°) and the large-ROM (> 12.5°) groups according to preoperatively index-level ROM. Clinical outcomes, including the Japanese Orthopedics Association (JOA), Neck Disability Index (NDI), and Visual Analogue Scale (VAS) scores, were evaluated. Radiological parameters, including cervical lordosis, disc angle (DA), global and segmental ROM, disc height (DH), and complications were measured. RESULTS: One hundred and twenty six patients, with a total of 132 arthroplasty segments were analyzed. There were 64 patients in the small-ROM and 62 in the large-ROM group. There were more patients diagnosed with cervical spondylosis in the small-ROM than in the large-ROM group (P = 0.046). Patients in both groups had significantly improved JOA, NDI, and VAS scores after surgery, but the intergroup difference was not significant. Patients in the small-ROM group had dramatic postoperative increase in cervical lordosis, global and segmental ROM (P < 0.001). However, there was a paradoxical postoperative decrease in global and segmental ROM in the large-ROM group postoperatively (P < 0.001). Patients in the small-ROM group had lower preoperative DH (P = 0.012), and a higher rate of postoperative heterotopic ossification (HO) (P = 0.037). CONCLUSION: Patients with preoperatively limited segmental ROM had severe HO, and achieved similar postoperative clinical outcomes as patients with preoperatively excessive segmental ROM. Patients with preoperatively limited segmental ROM showed a postoperative increase in segmental mobility, which decreased in patients with preoperatively excessive segmental ROM.


Assuntos
Degeneração do Disco Intervertebral , Substituição Total de Disco , Artroplastia/efeitos adversos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Seguimentos , Humanos , Degeneração do Disco Intervertebral/cirurgia , Amplitude de Movimento Articular , Estudos Retrospectivos , Substituição Total de Disco/efeitos adversos , Resultado do Tratamento
8.
Spine J ; 20(8): 1219-1228, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32445801

RESUMO

BACKGROUND CONTEXT: The development of bone loss (BL) at the operated level after cervical disc arthroplasty (CDA) has not been well recognized. The incidence of BL may be correlated with the prosthesis type. Currently, no study has reported the incidence of BL after CDA with the Prestige-LP disc, and this remains an active area of research. PURPOSE: To determine the incidence of BL after Prestige-LP CDA and evaluate the impact of BL on clinical and radiological outcomes. STUDY DESIGN: This is an observational study. PATIENT SAMPLE: A total of 396 patients were reviewed. OUTCOME MEASURES: The Japanese Orthopedics Association (JOA), Visual Analogue Scale (VAS), and Neck Disability Index (NDI) scores were evaluated. Cervical lordosis, disc angle, global and segmental range of motion (ROM), heterotopic ossification (HO), and BL were measured. METHODS: We retrospectively reviewed patients who underwent Prestige-LP disc from January 2008 to October 2018 at our institution. Clinical outcomes were evaluated using JOA, VAS, and NDI scores. Radiological variables, including cervical lordosis, disc angle, global and segmental ROM, HO, and BL, were retrieved. RESULTS: A total of 396 patients and 483 CDAs were evaluated. BL occurred in 56.6% of patients and 52.8% of CDA segments. Mild BL occurred in 30.2%, moderate BL in 37.3%, and severe BL in 32.5% of CDA segments. Notably, 88.2% of CDA segments developed BL within the first 3 months, and 19.1% of them progressed at 6 months. However, no progressive BL after 12 months was seen. About 50.2% of CDAs showed superior and inferior endplates involvement. The incidence of BL was associated with age, surgery type, level distribution, and incidence and grade of HO. Patients with BL had a better segmental ROM, but no relationships between patients with or without BL were found in clinical outcomes. CONCLUSIONS: BL was a common but self-limited phenomenon after CDA at the early postoperative stage. It occurred more often in relatively young age patients, two-level CDA, and C5/6 segment. However, patients suffering from BL showed no deterioration of the clinical outcomes, more exceptional motion preservation at the arthroplasty level, and lower incidence with a lower grade of HO.


Assuntos
Degeneração do Disco Intervertebral , Substituição Total de Disco , Artroplastia/efeitos adversos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Seguimentos , Humanos , Incidência , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/epidemiologia , Degeneração do Disco Intervertebral/cirurgia , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento
9.
Sci Rep ; 8(1): 3951, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29500441

RESUMO

Maturation-related changes in cell wall composition and the molecular mechanisms underlying cell wall changes were investigated from the apical, middle and basal segments in moso bamboo shoot (MBS). With maturation extent from apical to basal regions in MBS, lignin and cellulose content increased, whereas heteroxylan exhibited a decreasing trend. Activities of phenylalanine amonnialyase (PAL), cinnamyl alcohol dehydrogenase (CAD) and cinnamate-4-hydroxylase (C4H), which are involved in lignin biosynthesis, increased rapidly from the apex to the base sections. The comparative transcriptomic analysis was carried out to identify some key genes involved in secondary cell walls (SCW) formation underlying the cell wall compositions changes including 63, 8, 18, and 31 functional unigenes encoding biosynthesis of lignin, cellulose, xylan and NAC-MYB-based transcription factors, respectively. Genes related to secondary cell wall formation and lignin biosynthesis had higher expression levels in the middle and basal segments compared to those in the apical segments. Furthermore, the expression profile of PePAL gene showed positive relationships with cellulose-related gene PeCESA4, xylan-related genes PeIRX9 and PeIRX10. Our results indicated that lignification occurred in the more mature middle and basal segments in MBS at harvest while lignification of MBS were correlated with higher expression levels of PeCESA4, PeIRX9 and PeIRX10 genes.


Assuntos
Bambusa/crescimento & desenvolvimento , Proteínas de Plantas/genética , Brotos de Planta/metabolismo , RNA de Plantas/genética , Transcriptoma , Bambusa/genética
10.
Molecules ; 23(2)2018 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-29438302

RESUMO

To obtain novel structural antioxidants that have different antioxidant mechanisms, four 2-(alkylthio)-N-(4-(phenylamino)phenyl)acetamides 2a-d as dual functional antioxidants are designed, synthesized, and confirmed by ¹H-NMR, FTIR, MS, and elemental analysis. The antioxidant behavior of compounds 2a-d as additives of base oil triisodecyl trimellitate (TIDTM) is evaluated by non-isothermal and isothermal DSC analyses. The results showed all compounds can greatly increase the incipient oxidation temperature (IOT) and oxidation induction time (OIT) of TIDTM, especially, compound 2c exhibited an OIT value of 72.5 min at 230 °C, which is almost 28 times the length of TIDTM. Moreover, compounds 2a-d do not affect the tribological performance of TIDTM. The mechanism of antioxidants involved an intramolecular synergism are proposed. This work demonstrates compound 2c can be used as a novel potential antioxidant additive of TIDTM; in addition, it would inspire the emergence of highly potent antioxidants with different antioxidant mechanisms.


Assuntos
Acetamidas/síntese química , Antioxidantes/síntese química , Difenilamina/análogos & derivados , Lubrificantes/síntese química , Enxofre/química , Acetamidas/química , Antioxidantes/química , Fricção , Lubrificantes/química , Teste de Materiais , Oxirredução , Ácidos Tricarboxílicos/química
11.
J Integr Plant Biol ; 60(6): 514-528, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29393579

RESUMO

Xylan is the major plant hemicellulosic polysaccharide in the secondary cell wall. The transcription factor KNOTTED-LIKE HOMEOBOX OF ARABIDOPSIS THALIANA 7 (KNAT7) regulates secondary cell wall biosynthesis, but its exact role in regulating xylan biosynthesis remains unclear. Using transactivation analyses, we demonstrate that KNAT7 activates the promoters of the xylan biosynthetic genes, IRREGULAR XYLEM 9 (IRX9), IRX10, IRREGULAR XYLEM 14-LIKE (IRX14L), and FRAGILE FIBER 8 (FRA8). The knat7 T-DNA insertion mutants have thinner vessel element walls and xylary fibers, and thicker interfascicular fiber walls in inflorescence stems, relative to wild-type (WT). KNAT7 overexpression plants exhibited opposite effects. Glycosyl linkage and sugar composition analyses revealed lower xylan levels in knat7 inflorescence stems, relative to WT; a finding supported by labeling of inflorescence walls with xylan-specific antibodies. The knat7 loss-of-function mutants had lower transcript levels of the xylan biosynthetic genes IRX9, IRX10, and FRA8, whereas KNAT7 overexpression plants had higher mRNA levels for IRX9, IRX10, IRX14L, and FRA8. Electrophoretic mobility shift assays indicated that KNAT7 binds to the IRX9 promoter. These results support the hypothesis that KNAT7 positively regulates xylan biosynthesis.


Assuntos
Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Pentosiltransferases/genética , Proteínas Repressoras/metabolismo , Xilanos/biossíntese , Vias Biossintéticas/genética , Parede Celular/metabolismo , Perfilação da Expressão Gênica , Inflorescência/genética , Modelos Biológicos , Mutação/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Ligação Proteica/genética , Açúcares/metabolismo
12.
New Phytol ; 213(4): 1667-1681, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28164334

RESUMO

Recent studies indicate that the ETHYLENE RESPONSE FACTOR VII (ERF-VII) transcription factor is an important regulator of osmotic and hypoxic stress responses in plants. However, the molecular mechanism of ERF-VII-mediated transcriptional regulation remains unclear. Here, we investigated the role of ERF74 (a member of the ERF-VII protein family) by examining the abiotic stress tolerance of an ERF74 overexpression line and a T-DNA insertion mutant using flow cytometry, transactivation and electrophoretic mobility shift assays. 35S::ERF74 showed enhanced tolerance to drought, high light, heat and aluminum stresses, whereas the T-DNA insertion mutant erf74 and the erf74;erf75 double mutant displayed higher sensitivity. Using flow cytometry analysis, we found that erf74 and erf74;erf75 lines lack the reactive oxygen species (ROS) burst in the early stages of various stresses, as a result of the lower expression level of RESPIRATORY BURST OXIDASE HOMOLOG D (RbohD). Furthermore, ERF74 directly binds to the promoter of RbohD and activates its expression under different abiotic stresses. Moreover, induction of stress marker genes and ROS-scavenging enzyme genes under various stress conditions is dependent on the ERF74-RbohD-ROS signal pathway. We propose a pathway that involves ERF74 acting as an on-off switch controlling an RbohD-dependent mechanism in response to different stresses, subsequently maintaining hydrogen peroxide (H2 O2 ) homeostasis in Arabidopsis.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , NADPH Oxidases/metabolismo , Explosão Respiratória , Estresse Fisiológico , Arabidopsis/genética , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/genética , Sequência de Bases , Secas , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Genes Dominantes , Luz , Modelos Biológicos , Mutação/genética , Fenótipo , Pigmentação/efeitos da radiação , Folhas de Planta/fisiologia , Folhas de Planta/efeitos da radiação , Ligação Proteica/efeitos da radiação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Explosão Respiratória/efeitos da radiação , Estresse Fisiológico/genética , Estresse Fisiológico/efeitos da radiação , Ativação Transcricional/genética
13.
Bioorg Med Chem ; 23(7): 1395-401, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25766628

RESUMO

To identify new antifungal lead compound based on inhibitors of pyruvate dehydrogenase complex E1, a series of 5-iodo-1,4-disubstituted-1,2,3-triazole derivatives 3 were prepared and evaluated for their Escherichia coli PDHc-E1 inhibitory activity and antifungal activity. The in vitro bioassay for the PDHc-E1 inhibition indicated all the compounds exhibited significant inhibition against E. coli PDHc-E1 (IC50<21µM), special compound 3g showed the most potent inhibitory activity (IC50=4.21±0.11µM) and was demonstrated to act as a competitive inhibitor of PDHc-E1. Meanwhile, inhibitor 3g exhibited very good enzyme-selective inhibition of PDHc-E1 between pig heart and E. coli. The assay of antifungal activity showed compounds 3e, 3g, and 3n exhibited fair to good activity against Rhizoctonia solani and Botrytis cinerea even at 12.5µg/mL. Especially compound 3n (EC50=5.4µg/mL; EC90=21.1µg/mL) exhibited almost 5.50 times inhibitory potency against B. cinerea than that of pyrimethanil (EC50=29.6µg/mL; EC90=113.4µg/mL). Therefore, in this study, compound 3n was found to be a novel lead compound for further optimization to find more potent antifungal compounds as microbial PDHc-E1 inhibitors.


Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Piruvato Desidrogenase (Lipoamida)/antagonistas & inibidores , Triazóis/síntese química , Triazóis/farmacologia , Animais , Piruvato Desidrogenase (Lipoamida)/metabolismo , Complexo Piruvato Desidrogenase/antagonistas & inibidores , Complexo Piruvato Desidrogenase/metabolismo , Rhizoctonia/efeitos dos fármacos , Suínos
14.
Bioorg Med Chem ; 22(12): 3180-6, 2014 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-24800939

RESUMO

By targeting the ThDP binding site of Escherichia coli PDHc-E1, two new 'open-chain' classes of E. coli PDHc-E1 inhibitors, amide and urea derivatives, were designed, synthesized, and evaluated. The amide derivatives of compound 6d, with 4-NO2 in the benzene ring, showed the most potent inhibition of E. coli PDHc-E1. The urea derivatives displayed more potent inhibitory activity than the corresponding amide derivatives with the same substituent. Molecular docking studies confirmed that the urea derivatives have more potency due to the two hydrogen bonds formed by two NH of urea with Glu522. The docking results also indicate it might help us to design more efficient PDHc-E1 inhibitors that could interact with Glu522.


Assuntos
Amidas/química , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Escherichia coli/efeitos dos fármacos , Simulação de Acoplamento Molecular , Piruvato Desidrogenase (Lipoamida)/antagonistas & inibidores , Ureia/química , Sítios de Ligação , Domínio Catalítico , Escherichia coli/enzimologia , Ligação de Hidrogênio , Modelos Moleculares , Estrutura Molecular
15.
Bioorg Med Chem ; 22(1): 89-94, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24359707

RESUMO

As potential inhibitors of pyruvate dehydrogenase complex E1 (PDHc-E1), a series of 19 1-((4-amino-2-methylpyrimidin-5-yl)methyl)-5-methyl-N'-(substituent)benzylidene-1H-1,2,3-triazole-4-carbohydrazide 4 has been synthesized and tested for their PDHc-E1 inhibitory activity in vitro. Some of these compounds such as 4a, 4g, 4l, 4o, 4p, and 4q were demonstrated to be effective inhibitors by the bioassay of Escherichia coli PDHc-E1. SAR analysis indicated that the PDHc-E1 inhibitory activity could be further enhanced by optimizing the substituted groups in the parent compound. Molecular modeling study with compound 4o as a model was performed to evaluate docking. The results of modeling study suggested a probable inhibition mechanism.


Assuntos
Hidrazonas/síntese química , Piruvato Desidrogenase (Lipoamida)/antagonistas & inibidores , Complexo Piruvato Desidrogenase/antagonistas & inibidores , Hidrazonas/química , Hidrazonas/farmacologia , Modelos Moleculares , Complexo Piruvato Desidrogenase/farmacologia
16.
J Agric Food Chem ; 59(9): 4801-13, 2011 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-21452831

RESUMO

On the basis of the previous work for optimization of O,O-diethyl α-(substituted phenoxyacetoxy)alkylphosphonates, further extensive synthetic modifications were made to the substituents in alkylphosphonate and phenoxy moieties of the title compounds. New O,O-dimethyl α-(substituted phenoxyacetoxy)alkylphosphonates were synthesized as potential inhibitors of pyruvate dehydorogenase complex (PDHc). Their herbicidal activity and efficacy in vitro against PDHc were examined. Some of these compounds exhibited significant herbicidal activity and were demonstrated to be effective inhibitors of PDHc from three different plants. The structure-activity relationships of these compounds including previously reported analogous compounds were studied by examining their herbicidal activities. Both inhibitory potency against PDHc and herbicidal activity of title compounds could be increased greatly by optimizing substituent groups of the title compounds. O,O-Dimethyl α-(2,4-dichlorophenoxyacetoxy)ethylphosphonate (I-5), which acted as a competitive inhibitor of PDHc with much higher inhibitory potency against PDHc from Pisum sativum and Phaseolus radiatus than from Oryza sativa , was found to be the most effective compound against broadleaf weeds and showed potential utility as herbicide.


Assuntos
Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Herbicidas/síntese química , Herbicidas/farmacologia , Proteínas de Plantas/antagonistas & inibidores , Complexo Piruvato Desidrogenase/antagonistas & inibidores , Inibidores Enzimáticos/química , Herbicidas/química , Estrutura Molecular , Proteínas de Plantas/metabolismo , Plantas/efeitos dos fármacos , Plantas/enzimologia , Complexo Piruvato Desidrogenase/metabolismo , Relação Estrutura-Atividade
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