TY - JOUR
T1 - A porphycene-gentamicin conjugate for enhanced photodynamic inactivation of bacteria
AU - Nieves, Ingrid
AU - Hally, Cormac
AU - Viappiani, Cristiano
AU - Agut, Montserrat
AU - Nonell, Santi
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/4
Y1 - 2020/4
N2 - 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.
AB - 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.
KW - Amphiphilicity
KW - Antimicrobial resistance
KW - Photodynamic therapy
KW - Photosensitizer conjugates
KW - Porphycene
KW - Singlet oxygen
UR - https://www.scopus.com/pages/publications/85079551533
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000521282300008&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1016/j.bioorg.2020.103661
DO - 10.1016/j.bioorg.2020.103661
M3 - Article
C2 - 32086054
AN - SCOPUS:85079551533
SN - 0045-2068
VL - 97
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
M1 - 103661
ER -