Radiation-Induced Synthesis of a Minocycline-Derived Polycyclic Scaffold with Anti-Inflammatory and Antibacterial Effects.

Radiation is widely used as a powerful tool for inducing molecular transformation and expanding chemical diversity; however, its application in clinically relevant antibiotics remains limited. Minocycline (1), a clinically used tetracycline antibiotic, was subjected to gamma irradiation at doses of up to 30 kGy, resulting in the formation of a previously unreported radiation-induced derivative, minocyclinosin A (2). The structure of the newly generated compound was elucidated by comprehensive spectroscopic analyses, including one- and two-dimensional nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization mass spectrometry, which revealed extensive A-ring cleavage, degradation, and recyclization to form a unique cyclopenta[b]anthracene-type tetracycline scaffold. Biological evaluation revealed that minocyclinosin A exhibited enhanced anti-inflammatory activity by suppressing lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages, while maintaining antibacterial activity against skin inflammation-associated Staphylococcus species. High-performance liquid chromatography further demonstrated a clear dose-dependent molecular conversion, with irradiation at 30 kGy affording minocyclinosin A as the major product with a conversion efficiency of approximately 78.3%.