Design, Synthesis, and Biological Evaluation of Light-Activated Antibiotics.

The spatial and temporal control of bioactivity of small molecules by light (photopharmacology) constitutes a promising approach for study of biological processes and ultimately for the treatment of diseases. In this study, we investigated two different "caged" antibiotic classes that can undergo remote activation with UV-light at λ = 365 nm, via the conjugation of deactivating and photocleavable units through a short synthetic sequence. The two widely used antibiotics vancomycin and cephalosporin were thus enhanced in their performance by rendering them photoresponsive and thereby suppressing undesired off-site activity. The antimicrobial activity against ATCC 6633, ATCC 29213, ATCC 43300 (MRSA), ATCC 25922, and ATCC 27853 could be spatiotemporally controlled with light. Both molecular series displayed a good activity window. The vancomycin derivative displayed excellent values against Gram-positive strains after uncaging, and the next-generation caged cephalosporin derivative achieved good and broad activity against both Gram-positive and Gram-negative strains after photorelease.