A fine-tuned azobenzene for enhanced photopharmacology in vivo

Gutzeit, Vanessa A.; Acosta-Ruiz, Amanda; Munguba, Hermany; Häfner, Stephanie; Landra-Willm, Arnaud; Mathes, Bettina; Mony, Jürgen; Yarotski, Dzianis; Börjesson, Karl; Liston, Conor; Sandoz, Guillaume; Levitz, Joshua; Broichhagen, Johannes

doi:10.1016/j.chembiol.2021.02.020

Cited by 50 publications

(42 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the scope of photopharmacology remains restricted by the photochemical and biochemical limitations of its photoswitch scaffold repertoire [47] . Several limitations of the major scaffold azobenzene, including the diazene's susceptibility to thiol‐mediated degradation and its restricted scope of substituents compatible with bistable photoswitch performance, are well‐known [21] .…”

Section: Discussionmentioning

confidence: 99%

“…However, the scope of photopharmacology remains restricted by the photochemical and biochemical limitations of its photoswitch scaffold repertoire. [47] Several limitations of the major scaffold azobenzene, including the diazene's susceptibility to thiol‐mediated degradation and its restricted scope of substituents compatible with bistable photoswitch performance, are well‐known. [21] Non‐azobenzene photoswitches that avoid these drawbacks, such as dithienylethenes, hemithioindigos, and heterostilbenes, have only recently begun to be used in bioactive pharmacophores validated in cellular studies;[ 21 , 22 , 48 ] and the development of new photoswitch scaffolds is a valuable research goal in general.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pyrrole Hemithioindigo Antimitotics with Near‐Quantitative Bidirectional Photoswitching that Photocontrol Cellular Microtubule Dynamics with Single‐Cell Precision**

et al. 2021

View full text Add to dashboard Cite

We report the first cellular application of the emerging near‐quantitative photoswitch pyrrole hemithioindigo, by rationally designing photopharmaceutical PHTub inhibitors of the cytoskeletal protein tubulin. PHTubs allow simultaneous visible‐light imaging and photoswitching in live cells, delivering cell‐precise photomodulation of microtubule dynamics, and photocontrol over cell cycle progression and cell death. This is the first acute use of a hemithioindigo photopharmaceutical for high‐spatiotemporal‐resolution biological control in live cells. It additionally demonstrates the utility of near‐quantitative photoswitches, by enabling a dark‐active design to overcome residual background activity during cellular photopatterning. This work opens up new horizons for high‐precision microtubule research using PHTubs and shows the cellular applicability of pyrrole hemithioindigo as a valuable scaffold for photocontrol of a range of other biological targets.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pyrrole Hemithioindigo Antimitotics with Near‐Quantitative Bidirectional Photoswitching that Photocontrol Cellular Microtubule Dynamics with Single‐Cell Precision**

et al. 2021

View full text Add to dashboard Cite

show abstract

“…However,t he scope of photopharmacology remains restricted by the photochemical and biochemical limitations of its photoswitch scaffold repertoire. [47] Several limitations of the major scaffold azobenzene,i ncluding the diazenes susceptibility to thiol-mediated degradation and its restricted scope of substituents compatible with bistable photoswitch performance,a re well-known. [21] Non-azobenzene photoswitches that avoid these drawbacks,such as dithienylethenes, hemithioindigos,a nd heterostilbenes,h ave only recently begun to be used in bioactive pharmacophores validated in cellular studies; [21,22,48] and the development of new photoswitch scaffolds is avaluable research goal in general.…”

Section: Discussionmentioning

confidence: 99%

Pyrrole Hemithioindigo Antimitotics with Near‐Quantitative Bidirectional Photoswitching that Photocontrol Cellular Microtubule Dynamics with Single‐Cell Precision**

et al. 2021

View full text Add to dashboard Cite

We report the first cellular application of the emerging near-quantitative photoswitchp yrrole hemithioindigo,b yr ationally designing photopharmaceutical PHTub inhibitors of the cytoskeletal protein tubulin. PHTubsa llow simultaneous visible-light imaging and photoswitching in live cells,d elivering cell-precise photomodulation of microtubule dynamics,a nd photocontrol over cell cycle progression and cell death. This is the first acute use of ah emithioindigo photopharmaceutical for high-spatiotemporal-resolution biological control in live cells.I ta dditionally demonstrates the utility of near-quantitative photoswitches,b ye nabling ad arkactive design to overcome residual backgroundactivity during cellular photopatterning.This work opens up new horizons for high-precision microtubule researchusing PHTubsand shows the cellular applicability of pyrrole hemithioindigo as av aluable scaffold for photocontrol of ar ange of other biological targets.

show abstract

“…Several solutions have been proposed to address this limitation [ 22 ], including implantable LEDs [ 28 ], biodegradable electronics [ 29 ] and other wireless optofluidic devices [ 30 , 31 ]. Photoswitchable drugs that can be switched by light in the red to near infra-red region have also been investigated [ 20 , 32 , 33 ]. However, each approach suffers specific limitations.…”

Section: Introductionmentioning

confidence: 99%

Optical Fibre-Enabled Photoswitching for Localised Activation of an Anti-Cancer Therapeutic Drug

Palasis

Lokman

Quirk

et al. 2021

IJMS

View full text Add to dashboard Cite

Local activation of an anti-cancer drug when and where needed can improve selectivity and reduce undesirable side effects. Photoswitchable drugs can be selectively switched between active and inactive states by illumination with light; however, the clinical development of these drugs has been restricted by the difficulty in delivering light deep into tissue where needed. Optical fibres have great potential for light delivery in vivo, but their use in facilitating photoswitching in anti-cancer compounds has not yet been explored. In this paper, a photoswitchable chemotherapeutic is switched using an optical fibre, and the cytotoxicity of each state is measured against HCT-116 colorectal cancer cells. The performance of optical-fibre-enabled photoswitching is characterised through its dose response. The UV–Vis spectra confirm light delivered by an optical fibre effectively enables photoswitching. The activated drug is shown to be twice as effective as the inactive drug in causing cancer cell death, characterised using an MTT assay and fluorescent microscopy. This is the first study in which a photoswitchable anti-cancer compound is switched using an optical fibre and demonstrates the feasibility of using optical fibres to activate photoswitchable drugs for potential future clinical applications.

show abstract

A fine-tuned azobenzene for enhanced photopharmacology in vivo

Cited by 50 publications

References 83 publications

Pyrrole Hemithioindigo Antimitotics with Near‐Quantitative Bidirectional Photoswitching that Photocontrol Cellular Microtubule Dynamics with Single‐Cell Precision**

Pyrrole Hemithioindigo Antimitotics with Near‐Quantitative Bidirectional Photoswitching that Photocontrol Cellular Microtubule Dynamics with Single‐Cell Precision**

Pyrrole Hemithioindigo Antimitotics with Near‐Quantitative Bidirectional Photoswitching that Photocontrol Cellular Microtubule Dynamics with Single‐Cell Precision**

Optical Fibre-Enabled Photoswitching for Localised Activation of an Anti-Cancer Therapeutic Drug

Contact Info

Product

Resources

About