Background: Several metal-based molecules that display cytotoxicity against multiple cell lines have been pursued in an attempt to fight cancer and to overcome the typical side effects of drugs like cisplatin. In this scenario, ruthenium complexes have been extensively studied due to their activity in both in vitro and in vivo biological systems, including various cancer cell strains. Objective: We aimed to developed a method to synthesize novel [Ru(NO)(bpy) 2 L] 2+ complexes containing amino acid ligands by using an alternative Click Chemistry approach, namely the copper azide alkyne cycloaddition reaction (CuAAC reaction), to construct nitrosyl/nitrite complexes bearing a modified lysine residue. Methods: We synthesized a new ligand by Click Chemistry approach, and new compounds bearing the unprecedented ligand. Cytotoxicity was assessed by the classical MTT colorimetric assay. MCF-7 and MDA-MB-231 cells were used as breast cancer cells models. MCF-10 was used as a model of healthy cells. Results: Amino acid ligands related to N 3 -Lys(Fmoc) and the new pyLys were successfully synthesized by the diazotransfer reaction and the CuAAC reaction, respectively. The latter reaction involves coupling between N 3 - Lys(Fmoc) and 3ethynylpyridine. Both N 3 -Lys(Fmoc) and the new pyLys were introduced into the ruthenium bipyridine complex I, or cis[Ru II (NO)(NO 2 )(bpy) 2 ] 2+ , to generate the common nitro-based complex III, which was further converted to the final complex IV. Results of MTT assay proved the cytotoxic effect of cis-[Ru(NO)(bpy) 2 (pyLys)](PF 6 ) 2 against the mammalian breast cancer cells MCF-7 and MDA-MB231. Conclusion: The viability assays revealed that complex IV, bearing a NO group and a modified lysine residue, was able to release NO and croses tumor cell membranes. In this work, the Complex IV was the most active ruthenium bipyridine complex against the mammalian breast cancer cells MCF-7 and MDA-MB231: it was approximately twice as active as cisplatin, whilst complexes I–III proved to be less cytotoxic than complex IV. Additional tests using healthy MCF 10A cells showed that complexes II–IV were three- to sixfold less toxic than cisplatin, which suggested that complex IV was selective against cancer cells.
RESUMO A postura em pé durante o trabalho tem sido associada a sintomas musculoesqueléticos. Entretanto, há poucos estudos que avaliam o tempo em pé utilizando medidas objetivas. Assim, o objetivo deste estudo foi verificar se o tempo em pé no trabalho está associado com dor na coluna lombar e nos membros inferiores nos últimos sete dias e 12 meses em cuidadoras de idosos e trabalhadoras da limpeza. Trata-se de estudo transversal, em que o tempo em pé no trabalho foi quantificado por meio de inclinômetros fixados na coxa e na coluna vertebral, e os sintomas musculoesqueléticos foram avaliados por meio do Questionário Nórdico de Sintomas Osteomusculares. Os dados foram analisados por meio da correlação ponto bisserial (rpb) entre o tempo em pé no trabalho e a presença de sintomas musculoesqueléticos. As análises foram realizadas por meio do software SPSS e o nível de significância adotado foi de 5%. Verificou-se que as trabalhadoras passam a maior parte do tempo em pé paradas (41,3%) ou andando (39,3%). Houve correlação positiva entre a presença de sintoma na lombar e o tempo em pé (rpb=0,52; p<0,05) e correlação negativa entre o tempo andando e sintomas no quadril (rpb=−0,53; p<0,05) nos últimos 12 meses e o tempo correndo e sintomas no quadril (rpb=−0,43; p<0,05) e na coluna lombar (rpb=−0,43; p<0,05) nos últimos sete dias. O maior tempo em pé foi correlacionado com a presença de sintomas na lombar; enquanto o menor tempo andando e correndo foram correlacionados com a presença de sintomas no quadril e na coluna lombar.
Maintaining a standing posture during work has been associated with musculoskeletal symptoms. Few studies, however, assess the standing time using objective measures. Thus, this study aimed to verify whether standing time at work is associated with lower back and lower limb pain in the last seven days and last 12 months in caregivers of older adults and cleaners. This is a cross-sectional study. Standing time at work was quantified using inclinometers attached to the workers’ thigh and spine. Musculoskeletal symptoms were assessed using the Nordic Musculoskeletal Questionnaire. Data were analyzed using the point-biserial correlation coefficient (rpb) between standing time at work and the presence of musculoskeletal symptoms. The analyses were performed using the SPSS software, adopting 5% significance level. Workers spend most of their time standing still (41.3%) or walking (39.3%). The presence of symptoms in the lower back was positively correlated with standing time (rpb=0.52; p<0.05). Walking time was negatively correlated with symptoms at the hip in the last 12 months (rpb=−0.53; p<0.05) and running time with symptoms at the hip, in the last seven days, (rpb=−0.43; p<0.05) and the lower back (rpb=−0.43; p<0.05). Longer standing time was correlated with the presence of symptoms in the lower back. Meanwhile, less time walking and running were correlated with the presence of musculoskeletal symptoms in the hips and lower back.
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