Literature Talk Photocontrol of biological systems - Optical control of antibacterial activity 18/02/2014 APS

Transcription

1 Literature Talk Photocontrol of biological systems - Optical control of antibacterial activity 18/02/2014 APS

2 Photocontrolof biological systems Taken from: B. L. Feringa and coworkers, Chem. Rev. 2013, 113, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 1

3 Classical targets of antibacterial active compounds Taken from: C. Walsh, Nat. Rev. Microbiol. 2003, 1, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 2

4 Antibiotic resistances Causes: - evolutionary pressure (only low levels of preexisting antibioticresistant bacteria before the widespread use of antibiotics) APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 3

5 Antibiotic resistances Causes: - evolutionary pressure (only low levels of preexisting antibioticresistant bacteria before the widespread use of antibiotics) Mechanisms: - drug inactivation (e.g., β-lactamase) APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 4

6 Antibiotic resistances Causes: - evolutionary pressure (only low levels of preexisting antibioticresistant bacteria before the widespread use of antibiotics) Mechanisms: - drug inactivation (e.g., β-lactamase) - alteration of target side (e.g., alteration of PBP) APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 5

7 Antibiotic resistances Causes: - evolutionary pressure (only low levels of preexisting antibioticresistant bacteria before the widespread use of antibiotics) Mechanisms: - drug inactivation (e.g., β-lactamase) - alteration of target side (e.g., alteration of PBP) - alteration of metabolic pathway (e.g., no PABA required) APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 6

8 Antibiotic resistances Causes: - evolutionary pressure (only low levels of preexisting antibioticresistant bacteria before the widespread use of antibiotics) Mechanisms: - drug inactivation (e.g., β-lactamase) - alteration of target side (e.g., alteration of PBP) - alteration of metabolic pathway (e.g., no PABA required) - reduced drug accumulation (e.g., increased efflux) APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 7

9 Antibiotic resistances Causes: - evolutionary pressure (only low levels of preexisting antibioticresistant bacteria before the widespread use of antibiotics) Mechanisms: - drug inactivation (e.g., β-lactamase) - alteration of target side (e.g., alteration of PBP) - alteration of metabolic pathway (e.g., no PABA required) - reduced drug accumulation (e.g., increased efflux) One Example: - S. Loewenberg; India reports cases of totally drugresistant tuberculosis; The Lancet 2012, 379, 205. APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 8

10 Photopharmacology Taken from: B. L. Feringa and coworkers, J. Am. Chem. Soc. 2014, 136, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 9

11 Development of the photoswitchable agents Taken from: B. L. Feringa and coworkers, Nat. Chem. 2013, 5, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 10

12 UV properties of photoswitchable agent Compound 2 Taken from: B. L. Feringa and coworkers, Nat. Chem. 2013, 5, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 11

13 Syntheses of the photoswitchable agents Taken from: B. L. Feringa and coworkers, Nat. Chem. 2013, 5, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 12

14 Control of bacterial growth with photoswitchable agents 2 without irradiation (95% trans isomer) 2 irradiation at 365 nm (89% cis isomer) Taken from: B. L. Feringa and coworkers, Nat. Chem. 2013, 5, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 13

15 Biological activity of the photoswitchable agents Taken from: B. L. Feringa and coworkers, Nat. Chem. 2013, 5, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 14

16 Thermal cis-trans isomerization of the photoswitchable agent Thermal cis-trans isomerization of compound 2 Taken from: B. L. Feringa and coworkers, Nat. Chem. 2013, 5, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 15

17 Auto-inactivation of the photoswitchable agent Compound 2 activated at 365 nm at different times before incubation Taken from: B. L. Feringa and coworkers, Nat. Chem. 2013, 5, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 16

18 Pharmacodynamic study with the photoswitchable agent Bacteria incubated with compound 2 under different conditions Taken from: B. L. Feringa and coworkers, Nat. Chem. 2013, 5, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 17

19 Bacterial patterning with light Agar plate with compound 2 was incubated under light (365 nm) Taken from: B. L. Feringa and coworkers, Nat. Chem. 2013, 5, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 18

20 Acknowledgements Thank you very much for your attention! APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 19

21 Photoswitches introduced into biomolecules Taken from: B. L. Feringa and coworkers, Chem. Rev. 2013, 113, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 20

22 Synthesis of azobenzenes (I) APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 21

23 Synthesis of azobenzenes (II) Taken from: E. Merino, Chem. Soc. Rev. 2011, 40, APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 22

24 Bacterial growth APS 18/02/ Photocontrol of biological systems - Optical control of antibacterial activity (Literature Talk) 23