RESUMO
Solvothermal synthesis of multiple dihydropyrimidinones at a time has been developed in inexpensive and green bio-based solvent lactic acid without any additional catalysts or additives. By this method, thirty new dihydropyrimidinone derivatives were synthesized in two batches and characterized. All of the compounds were screened by Eg5 motor protein ATPase assay, and the positive compounds were tested against the Caco-2 cell line, HeLa cell line, L929 cell line and T24 cell line in vitro. Among them, compound C9 exhibited the best inhibitory activity against motor protein ATPase with an IC50 value of 30.25 µM and significant cytotoxic activity in the micromolar range against the cells above. The Lineweaver-Burk plot revealed that compound C9 was a mixed-type Eg5 inhibitor. A molecular modeling study using the Discovery Studio program was performed, where compound C9 exhibited good binding interaction with Eg5 motor protein ATPase, and this was consistent with the attained experimental results.
Assuntos
Antineoplásicos , Proliferação de Células/efeitos dos fármacos , Cinesinas , Pirimidinonas , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Cinesinas/antagonistas & inibidores , Cinesinas/metabolismo , Camundongos , Estrutura Molecular , Ligação Proteica , Pirimidinonas/síntese química , Pirimidinonas/química , Pirimidinonas/farmacologia , Relação Estrutura-AtividadeRESUMO
INTRODUCTION: Repeat ablation strategy for atrial fibrillation (AF) recurrence after multiple ablation procedures is known to be challenging. This study evaluated the insights of adjunctive ablation for epicardial arrhythmogenic substrates in those patients via a percutaneous epicardial approach. METHODS AND RESULTS: Thirty-five consecutive patients with AF/atrial tachycardia (AT) recurrence, who had two or more prior ablation procedures, were enrolled from September 2016 to December 2018. In addition to a standard endocardial approach, epicardial mapping and ablation were performed via a percutaneous subxiphoid access in the electrophysiology lab. Adjunctive epicardial ablations for left lateral ridge (LLR) were performed in 31 of 35 patients (88.6%) for efficient transmural lesions with pacing capture loss. Marshall Bundle (MB) potentials were documented on epicardial LLR in three patients and abolished by direct epicardial ablation. Bachmann's bundle (BB) was ablated as an epicardial conduction gap in four patients with a refractory anterior wall line. Two epicardial AT/AF triggers were detected followed by successful termination with epicardial ablation. No periprocedural complications occurred. About 23 of 35 patients (65.7%) remained free from AF/AT after 23.2 ± 9 months of the procedure. CONCLUSIONS: Patients with multiple failed prior AF procedures refractory to antiarrhythmic therapy might warrant a percutaneous epicardial mapping and ablation strategy, with adjunctive therapy for targeting LLR/MB, BB, and underlying epicardial triggers in addition to a standard endocardial approach.
Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter , Frequência Cardíaca , Pericárdio/cirurgia , Taquicardia Supraventricular/cirurgia , Potenciais de Ação , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Técnicas Eletrofisiológicas Cardíacas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pericárdio/fisiopatologia , Estudos Prospectivos , Recidiva , Reoperação , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Four new 5-hydroxyanthranilic acid related compounds, named anthocidins Aâ»D (1â»4), two known analogues n-lauryl 5-hydroxyanthranilate (5) and isolauryl 5-hydroxyanthranilate (6), together with benzamide (7), 3-hydroxy-4-methoxycinnamamide (8), and (3S-cis)-hexahydro-3-[(3,4-dihydroxyphenyl)methyl]pyrrolo[1,2-a]pyrazine-1,4-dione (9), were isolated from the fermentation broth of the marine-derived actinomycete, Streptomyces sp. HDa1, which was isolated from the gut of a sea urchin, Anthocidaris crassispina, collected from Hainan Island, China. The structures of these secondary metabolites were elucidated on the basis of their 1D and 2D-NMR and mass spectroscopic data, and anthocidin A was confirmed by single-crystal X-ray diffraction with Cu Kα radiation. Anthocidins Aâ»D (1â»4) feature an acetyl group substitution at the amino group and varying alkyl side chains at the carboxyl group of 5-hydroxyanthranilic acid, and compound 5 was isolated as a natural product for the first time. The cytotoxic and antibacterial activity of compounds 1â»9 were evaluated.
Assuntos
Actinobacteria/patogenicidade , Antibacterianos/isolamento & purificação , Ouriços-do-Mar/microbiologia , Streptomyces/patogenicidade , ortoaminobenzoatos/isolamento & purificação , Actinobacteria/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular , China , Cristalografia por Raios X , Fermentação , Modelos Moleculares , Estrutura Molecular , Streptomyces/química , ortoaminobenzoatos/química , ortoaminobenzoatos/farmacologiaRESUMO
BACKGROUND: The mechanisms underlying atrial fibrillation (AF) initiation and pulmonary vein isolation (PVI) effectiveness remain unclear. Ganglionated plexus (GPs) have been implicated in AF initiation and maintenance. In this study, we evaluated the impact of GP ablation in patients with pulmonary vein (PV) firing after PVI. METHODS: Patients with drug-refractory paroxysmal AF undergoing radiofrequency catheter ablation therapy with PVI were screened. Among 840 cases over a 3.75-year period, 12 cases were identified with persistent PV firing (left = 4 and right = 8) after PVI was achieved and left atrial sinus rhythm restored. Adjacent GP ablation was performed anatomically and followed if necessary by additional PV ablation. RESULTS: In eight patients, PV firing was terminated during GP ablation outside of the circumferential ablation line. In one patient, additional PV ablation resulted in cessation of PV firing and in the remaining three patients, firing could not be terminated by GP ablation or additional PVI. CONCLUSION: GP ablation outside of wide antral circumferential line frequently results in the cessation of rapid firing from electrically isolated PVs. These observations suggest that interactions between left atrium and PV beyond electrical conduction warrant consideration in AF mechanisms.
Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Gânglios Autônomos/cirurgia , Sistema de Condução Cardíaco/cirurgia , Veias Pulmonares/cirurgia , Cirurgia Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Pontos de Referência Anatômicos/diagnóstico por imagem , Fibrilação Atrial/diagnóstico por imagem , Mapeamento Potencial de Superfície Corporal/métodos , Feminino , Gânglios Autônomos/diagnóstico por imagem , Sistema de Condução Cardíaco/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Veias Pulmonares/diagnóstico por imagem , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the incidence and clinical outcome of adenosine triphosphate (ATP) plus isoproterenol (ISP)-induced non-pulmonary vein (PV) foci before and after circumferential PV isolation (CPVI) during index ablation in patients with paroxysmal atrial fibrillation (PAF). METHODS: In 80 consecutive patients undergoing catheter ablation for drug-refractory, symptomatic PAF at our hospital from April 2010 to January 2011, atrial fibrillation (AF) was provoked with ATP (20 mg) and ISP (20 µg/min) administration before and after CPVI. The spontaneous initiation of AF was mapped and recorded. RESULTS: Before ablation, AF mostly originating from PVs (PV vs. non-PV, 36/70 vs. 3/70; P<0.01) was induced in 39 patients with sinus rhythm. CPVI significantly suppressed AF inducibility; however, more non-PV foci were provoked (post-CPVI vs. pre-CPVI, 13/76 vs. 3/70; P=0.016). Patients with pre- and post-CPVI induced AF (n=49) were divided according to non-PV foci being induced (group N, n=17) or not (group P, n=32). After mean (19.2±8.2) months follow-up, 88.2% (15/17) and 65.6% (21/32) of patients in groups N and P, respectively, were free from AF recurrence (P=0.088). CONCLUSIONS: ATP+ISP administration effectively provokes non-PV foci, especially after CPVI in PAF patients. Although in this study difference did not achieve statistical significance, supplementary ablation targeting non-PV foci might benefit clinical outcome.