Synthesis and biological evaluation of novel 1,2,3,4-tetrahydro-ß-carboline derivatives as potential antibacterial agents.

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.

New Clerodane Diterpenoids from Tinospora capillipes with Antibacterial and Anti-Inflammatory Properties.

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 to 64 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.

[Effect of ginkgo biloba extract and dipyridamole on transcription and translation of inducible NO synthbase in rabbits after myocardial ischemia-reperfusion injury].

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.