RESUMEN
The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.
Asunto(s)
Antibacterianos , Carbolinas , Bacterias Gramnegativas , Bacterias Grampositivas , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Carbolinas/farmacología , Carbolinas/química , Carbolinas/síntesis química , Humanos , Relación Estructura-Actividad , Animales , Ratones , Bacterias Grampositivas/efectos de los fármacos , Estructura Molecular , Bacterias Gramnegativas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Hep G2 , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacosRESUMEN
Four new clerodane diterpenoids, namely tinocapills A-D (1-4), and one known analogue (5) were isolated from the roots of Tinospora capillipes in the present study. The structures of these new compounds, including their absolute configurations, were determined through a combination of detailed spectroscopic analysis and theoretical statistical approaches, including electronic circular dichroism (ECD) analyses and quantum mechanical (QM)-NMR methods. Additionally, the stereostructure of 5 was confirmed via X-ray diffraction analysis. Furthermore, all these isolates were evaluated for their antibacterial and anti-inflammatory activities. Compounds 1, 2 and 5 demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with MICs ranging from 4-64â µg/mL, and compounds 3 and 4 exhibited potential anti-inflammatory effects by suppressing LPS-induced TNF-α and NO releases in RAW264.7 cells.
RESUMEN
OBJECTIVE: To investigate the effects of Egb761, an extract of ginkgo biloba , and dipyridamole on inducible NO synthase (iNOS) in rabbits after myocardial ischemia-reperfusion injury. METHODS: After being established into ischemia-reperfusion injury model, 35 rabbits were divided randomly into 5 groups: Group A (the sham group), Group B (the model group), Group C (treated with dipyridamole 0.8 mg/kg), Group D (treated with Egb761, 40 mg/kg), and Group E (treated with Egb761 40 mg/kg combined with dipyridamole 0.8 mg/kg), all the medications were administered by intravenous injection 30 min after reperfusion. After administration, myocardial iNOS mRNA expression was detected by RT-PCR and western blot. RESULTS: Myocardial iNOS mRNA transcriptive expression in the 5 groups were A 0, B 157.11 +/- 17.73, C 202.6 +/- 21.84, D 356.13 +/- 24.18 and E 562.34 +/- 35.19 respectively, showing significant difference between the treated groups and group B (P <0.01). The translative expression of myocardial iNOS in the 5 groups were A 34.24 +/- 15.78, B 75.70 +/- 13.71, C 116.89 +/- 22.57, D 143.75 +/- 16.05 and E 195.09 +/- 22.25 respectively, showing significant difference between the treated groups and group B as well (P < 0.05, P < 0.01). CONCLUSION: Both Egb761 and dipyridamole could increase myocardial iNOS expression in transcriptive and translative levels in rabbits after myocardial ischemia-reperfusion injury, and the combined treatment of them shows a more significant effect.