Synthesis and Evaluation of the in vitro Antimicrobial Activity of Triazoles, Morpholines and Thiosemicarbazones.

BACKGROUND: Microbial infections is a global public health problem. The aim of this work was to synthesize and evaluate the antimicrobial activity of novel triazoles, morpholines and thiosemicarbazones. METHODS: Compounds were synthesized using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. The antimicrobial activity of these compounds against bacteria and yeast was evaluated by the broth microdilution method. RESULTS: The proposed route for synthesis gave high to moderate yields, moreover these compounds were successfully characterized by 1H NMR, 13C NMR and LC-MS. Antimicrobial testing indicated that the thiosemicarbazone and morphine derivatives had the best antimicrobial activity against the microorganisms tested with minimum inhibitory concentrations (MIC) between 0.29 and 5.30 µM. Thiosemicarbazone derivative (12) was able to inhibit the growth of C. tropicalis, with minimum fungicidal concentration (MFC) of 0.55 µM. In addition, this compound was active against E. coli, S. aureus and S. epidermidis, with MIC values ranging from 0.29 to 1.11 µM. Moreover, the morpholine derivative (15) had an MIC value of 0.83 µM against C. albicans and E. coli. CONCLUSION: We have efficiently synthesized a series of eleven novel triazoles, thiosemicarbazones and morpholine derivatives using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. Thiosemicarbazone derivative (12) showed promising antifungal and antibacterial activity and these findings suggest that this compound can be used as scaffolds to design new antimicrobial drugs.

Novos anticoagulantes orais (NOACs) na prevenção de acidente vascular encefálico (AVE) e fenômenos tromboembólicos em pacientes com fibrilação atrial / New oral anticoagulants (NOACs) in prevention of stroke brain and thromboembolic events in patients with atrial fibrillation

JUSTIFICATIVA E OBJETIVOS: Pacientes com fibrilação atrial (FA) estão mais propensos à ocorrência de eventos vasculares, como acidente vascular encefálico (AVE) e fenômenos tromboembólicos, sendo necessária anticoagulação oral. A varfarina, o anticoagulante mais utilizado, tem uma série de limitações referentes ao seu uso. Nesse contexto, foram desenvolvidos novos anticoagulantes orais (NOACs): inibidores da trombina (dabigatrana) e do fator Xa (rivaroxabana e apixabana). Essa revisão sistemática procurou elencar os principais resultados de Ensaios Clínicos Randomizados (ECRs) abordando o tema NOACs em pacientes com fibrilação atrial para a prevenção de acidente vascular encefálico e/ou fenômenos tromboembólicos. CONTEÚDO: Foram pesquisados Ensaios Clínicos Randomizados, cegos ou abertos, em indivíduos adultos, nas bases PubMed, Scopus, Web of Science, SciELO, LILACS e Cochrane CENTRAL. A avaliação da qualidade dos estudos foi feita utilizando a escala Downs & Black. Foram selecionados cinco Ensaios Clínicos Randomizados e descritos os seus resultados. A rivaroxabana se mostrou não inferior a varfarina no que diz respeito ao desfecho combinado embolismo sistêmico e acidente vascular encefálico, enquanto que a apixabana e a dabigatrana 150mg mostraram-se superiores. Todos os três medicamentos estiveram associados a menor incidência de hemorragia intracraniana quando comparado a varfarina. A apixabana mostrou perfil mais favorável em relação à ocorrência de qualquer sangramento. CONCLUSÕES: os Ensaios Clínicos Randomizados selecionados demonstraram a eficácia dos NOACs na prevenção de acidente vascular encefálicos e/ou embolismo sistêmico em pacientes com fibrilçao atrial. Contudo, são necessários mais estudos para preencher as lacunas do conhecimento quanto à eficácia e segurança desta nova classe de anticoagulantes orais.

BACKGROUND AND OBJECTIVES: Patients with atrial fibrillation (AF) are more likely to the occurrence of vascular events including stroke and thromboembolism systemic. Thus anticoagulation is necessary to prevent these events. Warfarin is the current gold standard but has a number of limitations regarding your use. In this context, new oral anticoagulants (NOACs) were developed: thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban and apixaban). The aim of this systematic review was to analyze the results of the main randomized clinical trials (RCTs) envolving NOACs in patients with atrial fibrillation for the prevention of stroke and/or thromboembolic events. CONTENTS: Double blinded or open label randomized clinical trials envolving patients with FA testing these drugs were researched in PubMed, Scopus, Web of Science, SciELO, LILACS and Cochrane CENTRAL. The quality assessment of studies used the Downs & Black Scale Five randomized clinical trials were selected, envolving 57.457 patients. Dabigatran, apixaban and rivaroxaban were at least non inferior to the warfarin in the outcome of stroke and systemic embolism. Apixaban and dabigatran 150mg were also superior than warfarin in efficacy. All three drugs were associated with a lower incidence of intracranial hemorrhage. Apixaban was related to lower risk of total bleeding. CONCLUSIONS: NOACs have efficacy to prevent AVE and systemic thromboembolism in patients with FA. However further studies are needed to resolve the issues that remain open and to provide more security to the use of these drugs in clinical practice.