P-536

P-536 is a ACE inhibitor that also inhibits herpes simplex virus HSV-1 thymidine kinase and Trypanosoma cruzi RNA polymerase. By inhibiting the renin-angiotensin system, downregulating the expression of AT1R and NOX4, and reducing oxidative stress (decreasing plasma hydrogen peroxide (H₂O₂) and 8-isoprostaglandin levels), P-536 effectively reduces systolic blood pressure and improves vascular reactivity. P-536 also inhibits the replication of DNA/RNA viruses such as HSV-1 by blocking nucleotide metabolism and nucleic acid synthesis, competitively inhibits RNA synthesis in Trypanosoma cruzi, and inhibits amastigote replication, thereby impeding its growth. P-536 is suitable for research on hypertension, insulin resistance, and Chagas disease^[1][2][3][4]. In Vitro:P-536 exhibits broad-spectrum antiviral activity. In their respective host cells, the CPE₅₀ against adenovirus type 5 is 20 μg/mL, the CPE₅₀ against HSV-1, poliovirus type 1 and encephalomyocarditis virus is 30 μg/mL, the CPE₅₀ against vaccinia virus is 70 μg/mL, and the CPE₅₀ against vesicular stomatitis virus, influenza A virus and measles virus is 100 μg/mL^[3].
P-536 (10-200 μg/mL; 48 h) potently inhibits the production of HSV-1 infectious units in HeLa cells, with 10 μg/mL inducing 1-log inhibition and 50 μg/mL inducing 3-log inhibition, and no cytotoxicity is observed at these concentrations^[3].
P-536 (100 μg/mL) blocks viral protein synthesis in HSV-1-infected HeLa cells when added at the onset of infection, but exerts no such effect when added 5 h post-infection^[3].
P-536 (50-200 μg/mL; 2 h) inhibits the glycosylation of viral proteins in HSV-1-infected HeLa cells. Its inhibitory effect on mannose and galactose incorporation is stronger than that on glucosamine, and the inhibitory effect is observed at all tested concentrations^[3].
P-536 (10-100 μg/mL; 8 h pre-treatment for RNA samples, 16 h pre-treatment for DNA samples) completely blocks the synthesis of HSV-1 TK mRNA in infected HeLa cells, and significantly reduces the accumulation of HSV-1 DNA at the concentration of 100 μg/mL^[3].
P-536 (100 μg/mL; 5 min; co-incubated with [³H]thymidine) blocks thymidine phosphorylation in HSV-1-infected HeLa cells, and dTMP is barely detectable in the cellular nucleotide pool^[3].
P-536 (150-200 μg/mL; 48 h (protein synthesis assay), 6 days (cell proliferation assay)) exhibits only extremely low cytotoxicity in mock-infected HeLa cells: the protein synthesis level at 200 μg/mL is consistent with that of the control group, and the inhibitory effect on cell proliferation at 150 μg/mL is less than 0.5-log^[3].
P-536 (5-10 μg/mL; 8-10 d) potently inhibits the growth of extracellular Trypanosoma cruzi epimastigotes in vitro, with an ID₅₀ of less than 5 μg/mL on the 8th day of culture^[4].
P-536 (25 μg/mL; 3 d) inhibits the growth of *Trypanosoma cruzi* amastigotes in J774G8 cells, with an ID₅₀ of 25 μg/mL on day 3 of culture^[4].
P-536 (50 μg/mL; 4 d) restores J774G8 cells infected with Trypanosoma cruzi: administration at the onset of infection prevents parasite-induced cell death and restores normal cell growth, while administration at 12 hours post-infection reduces the infection load^[4].
P-536 (10-100 μg/mL; 1 h) inhibits macromolecule synthesis in Trypanosoma cruzi epimastigotes; the inhibitory effect on RNA synthesis is the strongest at 100 μg/mL, but it does not induce significant plasma membrane leakage in Trypanosoma cruzi epimastigotes (only causes 17% of 86Rb+ efflux)^[4].