RESUMO
A series of thirty one novel 2-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-3-methylquinoxaline-1,4-dioxide (7a-l), 3-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-6-chloro-2-methylquinoxaline-1,4-dioxide (8a-l) and 2-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-6,7-dichloro-3-methylquinoxaline-1,4-dioxide (9a-g) analogues were synthesized, characterized using various analytical techniques and single crystal was developed for the compounds 8 g and 9f. Synthesized compounds were evaluated for in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain and two clinical isolates Spec. 210 and Spec. 192. The titled compounds exhibited minimum inhibitory concentration (MIC) ranging from 30.35 to 252.00 µM. Among the tested compounds, 8e, 8 l, 9c and 9d exhibited moderate activity (MIC = 47.6 - 52.0 µM) and 8a exhibited significant anti-tubercular activity (MIC = 30.35 µM). Furthermore, 8e, 8 l, and 9d were found to be less toxic against human embryonic kidney, HEK 293 cell lines. Finally, a docking study was also performed using MTB DNA Gyrase (PDB ID: 5BS8) for the significantly active compound 8a to know the exact binding pattern within the active site of the target enzyme.
Assuntos
Antituberculosos/química , Óxidos/química , Quinoxalinas/química , Triazóis/química , Antituberculosos/metabolismo , Antituberculosos/farmacologia , Sítios de Ligação , Domínio Catalítico , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , DNA Girase/química , DNA Girase/metabolismo , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Células HEK293 , Humanos , Testes de Sensibilidade Microbiana , Conformação Molecular , Simulação de Acoplamento Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Óxidos/metabolismo , Óxidos/farmacologia , Quinoxalinas/metabolismo , Quinoxalinas/farmacologia , Relação Estrutura-Atividade , Triazóis/metabolismo , Triazóis/farmacologiaRESUMO
OBJECTIVES: To compare the pain during anesthesia and during the no-scalpel vasectomy procedure for local infiltration anesthesia (LIA), LIA supplemented with spermatic cord block (LIA + SCB), and no needle jet anesthesia. METHODS: Bilateral no-scalpel vasectomy was performed in 323 patients during 2007. Of the 323 patients, 65 received LIA, 29 received LIA + SCB, and 227 received anesthesia using the no-needle technique with the MadaJet device. The level of pain during anesthesia administration and the subsequent procedural pain was documented for each technique using a pain scale of 0-10. RESULTS: Pain during the LIA + SCB procedure (mean 1.7 +/- 1.6) was significantly less than the pain during LIA (mean 3.3 +/- 2.3; P < .01). No statistically significant difference was found between the levels of pain experienced during LIA + SCB and no-needle jet anesthesia (P >> .01 and P >> .05, respectively). Intraoperative pain after LIA + SCB (mean 0.64 +/- 1.2) was significantly less than the intraoperative pain after LIA (mean 2.7 +/- 2.6; P <<< .01). Also, the intraoperative pain after LIA + SCB was significantly less than the intraoperative pain after no-needle jet anesthesia (mean 2.13 +/- 2.0; P <<< .01). CONCLUSION: LIA + SCB is an effective and better method of anesthesia compared with LIA alone or no-needle jet anesthesia for reducing the pain during vasectomy. Also, no difference was found in the pain levels during anesthesia for the LIA + SCB, LIA, and no-needle anesthesia techniques.