A porphycene-gentamicin conjugate for enhanced photodynamic inactivation of bacteria

Abstract A novel photoantimicrobial agent, namely 2–aminothiazolo[4,5-c]-2,7,12,17-tetrakis(methoxyethyl)porphycene (ATAZTMPo-gentamicin), conjugate has been prepared by a click reaction between the red-light absorbing 9–isothiocyanate-2,7,12,17-tetrakis(methoxyethyl)porphycene (9–ITMPo) and the antibiotic gentamicin. The conjugate exhibits submicromolar activity in vitro against both Gram-positive and Gram-negative bacteria (Staphylococcus aureus and Escherichia coli, respectively) upon exposure to red light and is devoid of any cytotoxicity in the dark. The conjugate outperforms the two components delivered separately, which may be used to enhance the therapeutic index of gentamicin, broaden the spectrum of pathogens against which it is effective and reduce its side effects. Additionally, we report a novel straightforward synthesis of 2,7,12,17–tetrakis(methoxyethyl) porphycene (TMPo) that decreases the number of steps from nine to six.