Acriflavine Hydrochloride is a multifaceted bioactive molecule with a partition coefficient (logD7.4) of 1.6, indicating moderate lipophilicity. It has demonstrated significant trypanocidal activity against Trypanosoma brucei, with increasing efficacy under higher concentrations and light exposure. Notably, it impacts the cross resistance of CHO cells resistant to colchicine (CHRC5) with a log CR value of 0.84.
The compound exhibits strong antimicrobial properties against a variety of bacterial strains, including Escherichia coli, Enterobacter cloacae, methicillin-resistant Staphylococcus aureus (MRSA), and Burkholderia pseudomallei. Its Minimum Inhibitory Concentrations (MIC) against these strains vary widely, reflecting differential efficacy based on specific genetic and resistance profiles. For example, MICs against multidrug-resistant E. coli with mutated GyrA gene exceed 128.0 µg/mL, while against other strains, MICs range from 2.0 to 4.0 µg/mL. The compound also affects the AcrAB-TolC efflux pump system, with an MIC of 400.0 µg/mL in Escherichia coli, and demonstrates efficacy against MRSA, with MIC50 at 12.5 µg/mL and MIC90 at 50.0 µg/mL.
Furthermore, Acriflavine Hydrochloride shows potent antiviral activity, including a 74.97% inhibition of SARS-CoV-2 induced cytotoxicity in Caco-2 cells at 10 µM, and a 98.59% inhibition of SARS-CoV-2 3CL-Pro protease at 20 µM. It also inhibits HIF-1 dimerization in HEK293 cells with an IC50 of 1000 nM.
In addition to its antimicrobial and antiviral activities, Acriflavine Hydrochloride impacts protein interactions and enzymatic activities, including Menin-MLL, BRCT-Phosphoprotein, Caspase-1, and Cytochrome P450 3A4. It also influences cellular responses such as ER Stress Response and DNA re-replication and exhibits antagonistic effects on proteins like MgcRacGAP.
Overall, Acriflavine Hydrochloride is a versatile compound with significant potential in antimicrobial, antiviral, and cellular bioactivity modulation applications..
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