Zinc(II)-Bisdipicolylamine Complex Bearing Agents for Selective Agglutination, Imaging, and Photodynamic Inactivation of Bacterial Cells


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Türkyilmaz S. , Şahin S., Özketen A. Ç. , Selvi H. T. , Akbulut D. , Erdem M., ...More

8th International Drug Chemistry Congress, Antalya, Turkey, 27 February - 01 March 2020, pp.216

  • Publication Type: Conference Paper / Summary Text
  • City: Antalya
  • Country: Turkey
  • Page Numbers: pp.216

Abstract

The constant emergence of bacterial strains resistant to antibiotics in clinical use is a critical threat to public health.2 Recognition groups that selectively target bacterial cells may enhance the efficacy of antibiotic agents when coupled to them. Zinc(II) bisdipicolylamine (Zn2BDPA) complexes have emerged as efficient bacterial targeting groups that selectively bind to negatively charged phosphate amphiphiles (e.g. phosphatidylglycerol, lipoteichoic acid, and lipid A) found in bacterial cell membranes and walls (Figure 1, Panel A). We have developed Zn2BDPA bearing liposomal and dendrimeric systems, and optical and nuclear imaging agents for the selective binding, agglutination, and imaging of bacterial cells.3a-d We have also developed Zn2BDPA-porphyrin conjugates as selective antibacterial photodynamic inactivation (PDI) agents (Figure 1, Panel B). We have demonstrated that these agents can generate singlet oxygen when irradiated with visible light (>400 nm) in the presence of O2. We have also demonstrated that these agents bind to bacterial cell membranes (Figure 2, Panel C; GFP expressing E. coli green, Zn2BDPA-porphyrin conjugate red). The antibacterial efficiency of the iodo bearing derivative was evaluated against a number of bacterial strains and PDI (both Type I and Type II) in addition to some dark toxicity was observed for most of them. For instance, 99.99% of E. coli cells (5x106 CFU/ml) were inactivated upon irradiation with visible light in the presence of 1 M of the iodo Zn2BDPA-porphyrin derivative and atmospheric oxygen. This agent showed no dark toxicity (MTT assay) against mammalian cells (MCF7) in the 0.25-10 M concentration range. 


Acknowledgement: We gratefully acknowledge partial support for this work from TÜBİTAK (215Z052, 114C041), Istanbul University (53435, 45772), and Middle East Technical University (2667).

Footnotes and References 

1) Undergraduate student researchers.

2) https://www.who.int/news-room/detail/17-01-2020-lack-of-new-antibiotics-threatens-global-efforts-to-contain-drug-resistant-infections (accessed 31.01.2020)

3) a. Turkyilmaz, S.; Rice, D.R.; Palumbo, R.; Smith B.D. Org. Biomol. Chem. 2014, 12, 5645-5655; b. Rice, D.; Plaunt, A. J.; Turkyilmaz, S.; Smith, M.; Wang, Y.; Rusckowski, M.; Smith B.D. Mol. Imaging Biol. 2015, 17, 204-213; c. Xiao, S.; Turkyilmaz, S.; Smith, B.D. Tetrahedron Lett. 2013, 54, 861-864; d. Xiao, S.; Abu-Esba, L.; Turkyilmaz, S.; White, A.G.; Smith B.D. Theranostics 2013, 3 (9), 658-666.