Loureirin B

There is an urgent need to develop new anti-tuberculosis (anti-TB) drugs to tackle drug-resistant strains of Mycobacterium tuberculosis (M.tb). Whereas antimicrobial peptides (AMPs) have received attention because of their antibacterial properties, oligo-N-substituted glycines (peptoids) are now seen as favorable alternatives to AMPs because they are more stable and less vulnerable to protease degradation, less expensive to produce, and better suited to potential pharmaceutical adoption and development. In this work, therefore, we designed, synthesized, and screened 22 new α- and β-peptoids against drug susceptible M. tb strain H37Rv using the Microplate Alamar Blue assay (MABA) to evaluate minimum inhibitory concentration (MIC). Eight compounds (JC5, MM2, MM5, MM9, MM10, MM11, JF11, and JF13) had MICs of less than 10 μg/ml, the most potent of which were JC5 and MM2, with MICs of 1.48 μg/ml and 2.97 μg/ml, respectively. JC5 and MM2 also retained potency against strains mono-resistant to isoniazid and rifampin, and against five of the global M. tb clade representatives. Furthermore, peptoids JC5 and MM2 showed minimum bactericidal concentration (MBC) of 3.02 μg/ml and 5.48 μg/ml respectively. Intracellular activity by luminescence showed a macrophage EC90 of less than 10 μg/ml for both JC5 and MM2. In addition, both compounds showed remarkable narrow spectrum activity. Selectivity with respect to Vero cells was modest but sufficient to consider these classes of alpha and beta-peptoids as good leads for further development of anti-TB drugs.

Dragon's Blood (DB), a natural resin extracted from Dracaena cochinchinensis, exhibits anti-inflammatory and neuroprotective properties, but its efficacy and underlying mechanisms in ischemic stroke remain to be fully elucidated. In this study, the neuroprotective effects of DB were evaluated using both transient and permanent middle cerebral artery occlusion (tMCAO and dMCAO) models in mice. DB treatment significantly reduced infarct volume, improved neurological outcomes, and alleviated neuronal apoptosis. Transcriptomic profiling revealed that DB modulated signaling pathways related to neuroinflammation, blood-brain barrier (BBB) integrity, and actin cytoskeleton remodeling. These effects were supported by decreased Evans blue leakage, upregulated expression of tight junction proteins (ZO-1 and Claudin-5), and suppressed pro-inflammatory mediators including TNF-α, IL-1β, IL-6, and iNOS, along with increased levels of Arg-1 and IL-10. Moreover, DB downregulated disulfidptosis-related genes such as Flna, Iqgap1, Tln1, and Myh9. Molecular docking further suggested that Loureirin B, a major active constituent of DB, binds strongly to these targets, indicating a potential mechanistic link. These findings suggest that DB confers multi-target neurovascular protection in ischemic stroke by regulating inflammation, preserving BBB function, and inhibiting disulfidptosis, supporting its potential as a candidate for therapeutic development.