1.D.278. The Amphipathic Pyranochromene Derivative (APD) Family
Pyranochromene derivatives are membrane targeting antibacterials against Gram-positive bacteria (Wang et al. 2024). They represent a class of novel amphipathic pyranochromene derivatives that were designed and synthesized by mimicking the amphiphilic characteristics of AMPs. Bioactivity screening identified a lead compound 5a with broad-spectrum antibacterial activity against Gram-positive stains (MICs = 1-4 μg/mL) and low hemolytic toxicity (HC50 = 111.6 μg/mL). Additionally, compound 5a displayed rapid bactericidal action, and is unlikely to induce bacterial resistance. Mechanistic investigation further demonstrated that compound 5a is able to disrupt the transmembrane potential and increased membrane permeability of S. aureus, which in turn causes leakage of cell contents such as DNA and proteins, ultimately leading to bacterial death. These findings indicated that compound 5a is a promising lead to combat bacterial infection caused by Gram-positive bacteria (Wang et al. 2024).