Synthesis, ADMET Prediction, and Antitumor Profile of Phenoxyhydrazine- 1,3-thiazoles Derivatives.

BACKGROUND: Cancer is one of the most important barriers to increasing life expectancy in all countries in the 21st century. Investigations of new anti-cancer drugs with low side effects are an urgent demand for medicinal chemists. Considering the known antitumor and immunomodulatory activity of thiazoles, this work presents the synthesis and antineoplastic activity of new thiazoles. METHODS: The 22 new compounds (2a-v) were synthesized from different thiosemicarbazones and 2-bromoacetophenone. The compounds were evaluated on: MOLT-4, HL-60, HL-60/MX1, MM1S, SKMEL-28, DU145, MCF-7, and T47d. RESULTS: Compound 2b induced cellular viability on MOLT-4 (37.1%), DU145 (41.5%), and HL- 60/MX1 (58.8%) cells. On MOLT-4 cells, compound 2b exhibited an IC50 of 8.03 µM, and against DU145 cells, an IC50 of 6.04µM. Besides, at IC50 and fold of IC50, 20% to 30% of dead cells were found, most due to necrosis/late apoptosis. Most compounds no showed cytotoxicity against fibroblast cells L929 at the concentrations tested. The compound did not alter the cell cycle of DU145 cells when compared to the negative control. Therefore, compound 2b stands out against DU145 and MOLT-4 cells. CONCLUSION: Our study reinforced the importance of 1,3-thiazoles nuclei in antitumor activity. In addition, derivative 2b stands out against DU145 and MOLT-4 cells and could be a starting point for developing new antineoplastic agents.

Multi-target compounds acting in cancer progression: Focus on thiosemicarbazone, thiazole and thiazolidinone analogues.

Currently, cancer and its progression to metastasis result in a large number of deaths. The lack of new drugs, appropriate clinical trials for metastasis preventive drugs and incomplete understanding of the molecular machinery are the major obstacles in metastasis prevention and treatment. On the other hand, thiosemicarbazones and their bioisosteres, thiazole and thiazolidinone are recurring in a wide range of biologically active compounds that reach different targets within tumor context and represent a promising start point to access potential candidates in metastatic cancer. Therefore, the search for new lead compounds showing highest anticancer potency and less adverse effects is the major challenger in drug discovery. The search was based from 1994 to 2018, focusing on thiosemicarbazone, thiazole and thiazolidinone cores that allowed us to discuss how the three multi-target motifs have been used for the target-based design and development of anticancer agents. In the lasts years, thiosemicarbazone, thiazole, and thiazolidinone cores are recurrent in many approaches for cancer therapy. In our search, it was verified that due to its biodiversity and versatility the anticancer potential of such structures has been assigned to distinct mechanisms reinforcing the value of these cores in the anticancer drug development. The present article aims point out the current application of thiosemicarbazone, thiazole and thiazolidinone cores in the design of anticancer agents within tumor progression, acting via varied targets such as cathepsins, NDRG1 gene and kinases, showing in vitro tests, in vivo tests and clinical trials. In our search it was possible to verify that thiazole is the most studied and the most important of the three structures. Therefore, we hope to provide new insights and valuable inspiration in the research of new drugs and development and contribute to the management of cancer.

Analysis of YouTube videos about urinary catheterization technique of male delay / Análisis de los vídeos en YouTube sobre la técnica de cateterismo vesical por retención de orina en el hombre / Análise de vídeos do YouTube sobre a técnica de cateterismo urinário de demora masculino

Objective.To analyze the execution of urinary catheterization technique of male delay in YouTube videos. Methods. This is an exploratory research with a quantitative approach, performed using the YouTube sharing site. The search of the videos was conducted in September 2014, using the controlled descriptor "urinary catheterization". Results. 32 videos were analyzed, none were in accordance with the standards established in the literature; among the main errors highlight the absence of hand washing (78.1%), the absence of the medical recording (71.8%), the absence of cleaning and drying of the patient at the end of the procedure (71.8%), the incorrect technique during antisepsis (62.5%) and the absence of gloves changes (59.3%). Conclusion. Although the YouTube sharing video site is currently a widespread tool, there is an absence of videos that reproduce the technique according to what is recommended in the literature.

Objetivo.Analizar la ejecución de la técnica de cateterismo vesical por retención de orina en el hombre en los vídeos en YouTube. Métodos. Estudio exploratório de abordaje cuantitativo realizado en el sitio web YouTube. Se realizó uma búsqueda de los vídeos en septiembre de 2014 utilizando el descriptor controlado "cateterismo urinario". Resultados. Fueron analizados 32 vídeos, de los cuales ninguno estaba de acuerdo con los patrones establecidos por la literatura. Entre los principales errores encontrados se destacan: la ausencia de lavado de las manos (78.1%), falta de registro en la historia clínica (71.8%), ausencia de limpieza y secado del paciente al terminar del procedimento (71.8%), técnica incorrecta durante la antisepsia (62.5%) y falta de cambio de guantes (59.3%). Conclusión. Aunque sitio web YouTube es una herramienta ampliamente difundida atualmente, hay carencia de vídeos que reproduzcan la técnica de acuerdo con los patrones establecidos en la literatura.

Objetivo.Analisar a execução da técnica de cateterismo urinário de demora masculino nos vídeos do YouTube. Métodos. Trata-se de uma pesquisa exploratória, de abordagem quantitativa, realizada no sítio de compartilhamento YouTube. A busca dos vídeos foi realizada em setembro de 2014, utilizando-se o descritor controlado "cateterismo urinário". Resultados. Foram analisados 32 vídeos, dos quais nenhum estava de acordo com os padrões estabelecidos pela literatura; dentre os principais erros encontrados, destacam-se a ausência de lavagem das mãos (78.1%), a falta de registro no prontuário (71.8%), a ausência de limpeza e secagem do paciente no término do procedimento (71.8%), a técnica incorreta durante antissepsia (62.5%) e a falta de troca de luvas (59.3%). Conclusão. Apesar de o sítio de compartilhamentos de vídeo YouTube ser uma ferramenta amplamente difundida atualmente, há uma carência de vídeos que reproduzam a técnica de acordo com o que é preconizado na literatura.

Analysis of YouTube videos about urinary catheterization technique of male delay.

OBJECTIVE: To analyze the execution of urinary catheterization technique of male delay in YouTube videos. METHODS: This is an exploratory research with a quantitative approach, performed using the YouTube sharing site. The search of the videos was conducted in September 2014, using the controlled descriptor "urinary catheterization". RESULTS: 32 videos were analyzed, none were in accordance with the standards established in the literature; among the main errors highlight the absence of hand washing (78.1%), the absence of the medical recording (71.8%), the absence of cleaning and drying of the patient at the end of the procedure (71.8%), the incorrect technique during antisepsis (62.5%) and the absence of gloves changes (59.3%). CONCLUSION: Although the YouTube sharing video site is currently a widespread tool, there is an absence of videos that reproduce the technique according to what is recommended in the literature.