Reduction of photoswitched, nitrogen bridged N-acetyl diazocines limits inhibition of 17βHSD3 activity in transfected human embryonic kidney 293 cells

Wages, F.; Lentes, Pascal; Griebenow, Thomas; Herges, Rainer; Peifer, Christian; Maser, Edmund

doi:10.1016/j.cbi.2022.109822

Cited by 7 publications

(7 citation statements)

References 38 publications

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“…A second example of scaffold hopping of an atypical (E)-like core has been reported very recently for the optical control of 17β-hydroxysteroid dehydrogenase type 3 (17βHSD3). [138] A series of tetrahydrodibenzazocine inhibitors inspired the design of diazocine analogs due to their striking similarity. Overlap of the the ligand structures showed that the metastable (E)-isomer could adopt a similar spatial arrangment to the parent compound, while the outof-plane geometry of the (Z)-isomer was different.…”

Section: Methodsmentioning

confidence: 99%

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Rational Design in Photopharmacology with Molecular Photoswitches

et al. 2023

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Photopharmacology is an attractive approach for achieving targeted drug action with the use of light. In photopharmacology, molecular photoswitches are introduced into the structure of biologically active small molecules to allow for the optical control of their potency. Going beyond trial and error, photopharmacology has progressively applied rational drug design methodologies to devise light-controlled bioactive ligands. In this review, we categorize photopharmacological efforts from the standpoint of medicinal chemistry strategies, focusing on diffusible photochromic ligands modified with photoswitches that operate through E-Z bond isomerization. In the vast majority of cases, photoswitchable ligands are designed as analogs of existing compounds, through a variety of approaches. By analyzing in detail a comprehensive list of instructive examples, we describe the state of the art and discuss future opportunities for rational design in photopharmacology.

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Section: Methodsmentioning

confidence: 99%

“…A second example of scaffold hopping of an atypical ( E )‐like core has been reported very recently for the optical control of 17β‐hydroxysteroid dehydrogenase type 3 (17βHSD3) [138] . A series of tetrahydrodibenzazocine inhibitors inspired the design of diazocine analogs due to their striking similarity.…”

Section: Analog Designmentioning

confidence: 99%

Rational Design in Photopharmacology with Molecular Photoswitches

et al. 2023

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“…[1][2][3][4][5][6][7][8][9][10][11][12][13] As a result, diazocines have found use in emerging elds, such as stimuli-responsive systems, [14][15][16][17][18][19] photoactuation, 20 and most notably, photopharmacology. [21][22][23][24][25][26][27][28] Unlike conventional azobenzene, whose triplet state properties have been investigated since the 1960s, 29 no studies on the triplet states of diazocine molecules have been published. Knowledge of the triplet state properties has been exploited to achieve sensitized photoswitching of conventional azobenzenes 30 (Scheme 1) in addition to other classes of molecules, such as diarylethenes, 31,32 overcrowded alkenes, 33 stilbenes, 34,35 indigos 36 and norbornadienes.…”

Section: Introductionmentioning

confidence: 99%

“…1–13 As a result, diazocines have found use in emerging fields, such as stimuli-responsive systems, 14–19 photoactuation, 20 and most notably, photopharmacology. 21–28…”

Section: Introductionmentioning

confidence: 99%

Triplet sensitization enables bidirectional isomerization of diazocine with 130 nm redshift in excitation wavelengths

et al. 2023

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“…Diazocines also exhibit more efficient photoswitching using longer excitation wavelengths and possess higher quantum yields. [1][2][3][4][5][6][7][8][9][10][11][12][13] As a result, diazocines have found use in emerging fields, such as stimuli-responsive systems, [14][15][16][17][18][19] , photoactuation, 20 and most notably, photopharmacology [21][22][23][24][25][26][27][28] . Unlike conventional azobenzene, whose triplet state properties have been investigated since the 1960s, 29 no studies on the triplet states of diazocine molecules have been published.…”

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confidence: 99%

Triplet-Sensitized Bidirectional Isomerization of Bridged Azobenzene

Isokuortti

Griebenow²,

Glasenapp³

et al. 2023

Preprint

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Diazocine is a bridged azobenzene with both phenyl rings connected by a CH2-CH2 group. Despite this rather small structural difference, diazocine exhibits improved properties over azobenzene as a photoswitch, such as high switching efficiencies, very high quantum yields, switching wavelengths in the visible range, and most importantly, the fact that it is more stable in the Z configuration, which is particularly expedient in photopharmacology and mechanophore applications. According to our studies presented here, another advantage over conventional azobenzene is now added. In contrast to azobenzenes and other photochromes, diazocine can be switched with two different triplet sensitizers present at the same time in both directions: Z→E as well as E→Z. Experimental and theoretical (CASPT2) studies of triplet excitation energies provide an explanation for this fact. The triplet energies in Z and E azobenzene are almost equal, which prevents selective sensitization of either isomer. In diazocine, the two excitation energies are well-separated, so they can be accessed selectively. Besides offering fundamental physical insight to diazocines, an emerging class of photoswitches, our work opens up a number of potential avenues for utilizing them for example in photopharmacology and smart materials design due to the significant redshift of excitation wavelengths to from blue to green (Z→E) and green to far-red (E→Z), which triplet sensitization offers.

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Reduction of photoswitched, nitrogen bridged N-acetyl diazocines limits inhibition of 17βHSD3 activity in transfected human embryonic kidney 293 cells

Cited by 7 publications

References 38 publications

Rational Design in Photopharmacology with Molecular Photoswitches

Rational Design in Photopharmacology with Molecular Photoswitches

Triplet sensitization enables bidirectional isomerization of diazocine with 130 nm redshift in excitation wavelengths

Triplet-Sensitized Bidirectional Isomerization of Bridged Azobenzene

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