Synthesis of (-) - 6, 6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment

Chagas disease is a public health problem affecting approximately seven million people worldwide. Thus, there is a need to discover drugs for the adequate treatment of this disease because currently available drugs have serious side effects. Therefore, this study aimed to evaluate the in vitro trypanocidal activity of (-)-6,6'-dinitrohinokinin, obtained from the partial synthesis of (-)-hinokinin, on the trypomastigotes and amastigotes forms. For the trypomastigote assay, blood was collected from mice infected with Trypanosoma cruzi through cardiac puncture at the parasitemic peak. The results show that (-)-6,6'-dinitrohinokinin was effective against the trypomastigote forms, presenting an IC50 of 19.83 µM and lysis percentage values ​​of 78.4% and 69.4% at concentrations of 200 and 100 µM, respectively. Molecular docking calculations indicate that (-)-6,6'-dinitrohinokinin favorably interacts with the amino acids present in the active site of the protein trypanothione reductase, a typical target for anti-trypanosomal drug development. According to the results, the (-)-6,6'-dinitrohinokinin showed more significant trypanocidal activity with IC50 of 1.83 µM than benzonidazole positive control with IC50 of 53.2 µM, showing to be a prototype molecule promising for the development of a new antiparasitic drug.

Diagnóstico e tratamento da dimensão vertical de oclusão diminuída: utilização de prótese parcial removível atípica (PPR tipo "overlay") / Treatment of reduced occlusion vertical dimension

O desgaste generalizado das superfícies oclusais dos dentes acarreta no colapso da dimensão vertical de oclusão do paciente e, conseqüentemente, em prejuízos na estética, função e fonética do paciente. O presente artigo descreve a confecção de uma PPR tipo overlay superior e inferior que recobre as superfícies oclusais dos dentes, restabelecendo a dimensão vertical do paciente. Este tipo de prótese é indicado principalmente em casos de desgaste severo das superfícies oclusais ou em casos de mordida aberta com grande trespasse vertical. As principais vantagens deste tipo de tratamento são a reversibilidade, bem como custo e tempo operacional reduzidos quando comparado com tratamentos mais complexos. Após o término do tratamento, o paciente mostrou-se altamente satisfeito com a recuperação das atividades funcionais anteriormente comprometidas.