RESUMO
A novel BODIPY derivative was designed for biomedical applications. Its mono-quaternized structure ensured its water-solubility and suitable amphiphilicity. Showing no singlet oxygen generation to avoid damage to healthy cells, this new derivative proved to be an extremely promising antimicrobial agent, with activity equal or superior to ampicillin against MRS Staphylococcus strains with no short-term resistance issue. Its activity against MSS Staphylococcus strains was largely superior to those of ampicillin and reached the activity of vancomycin against MSS S. epidermidis. This latter result is in particular extremely promising for the treatment of hospital-acquired infections. Also the fluorescence properties of BODIPY allowed imaging of the uptake.
Assuntos
Antibacterianos/farmacologia , Compostos de Boro/química , Compostos de Boro/farmacologia , Staphylococcus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Compostos de Boro/síntese química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Staphylococcus/classificação , Relação Estrutura-AtividadeRESUMO
The design and synthesis of a phthalocyanine--Gd-DOTA conjugate is presented to open the way to novel molecular theranostics, combining the properties of MRI contrast imaging with photodynamic therapy. The rational design of the conjugate integrates isomeric purity of the phthalocyanine core substitution, suitable biocompatibility with the use of polyoxo water-solubilizing substituents, and a convergent synthetic strategy ended by the use of click chemistry to graft the Gd-DOTA moiety to the phthalocyanine. Photophysical and photochemical properties, contrast imaging experiments and preliminary in vitro investigations proved that such a combination is relevant and lead to a new type of potential theranostic agent.