<p>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 thus suppressing undesired off-site activity. The
antimicrobial activity against <i>Bacillus subtilis</i> ATCC 6633, <i>Staphylococcus aureus</i> ATCC 29213, <i>S.
aureus</i> ATCC 43300 (MRSA), <i>Escherichia coli</i> ATCC 25922, and <i>Pseudomonas
aeruginosa</i> 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.</p>
Design, synthesis and biological evaluation of 4-benzoyl-1-dichlorobenzoylthiosemicarbazides as potent Gram-positive antibacterial agents
