دورية أكاديمية
Rational Design of Photochromic Analogues of Tricyclic Drugs
| العنوان: | Rational Design of Photochromic Analogues of Tricyclic Drugs |
|---|---|
| المؤلفون: | Riefolo, Fabio, Sortino, Rosalba, Matera, Carlo, Claro Izaguirre, Enrique, Preda, Beatrice, Vitiello, Simone, Traserra, Sara, Jiménez, Marcel, Gorostiza Langa, Pablo Ignacio |
| المصدر: | Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC)) |
| بيانات النشر: | ACS Publications |
| سنة النشر: | 2021 |
| المجموعة: | Dipòsit Digital de la Universitat de Barcelona |
| مصطلحات موضوعية: | Medicaments, Neurotransmissors, Fotoquímica, Drugs, Neurotransmitters, Photochemistry |
| الوصف: | Tricyclic chemical structures are the core of many important drugs targeting all neurotransmitter pathways. These medicines enable effective therapies to treat from peptic ulcer disease to psychiatric disorders. However, when administered systemically, they cause serious adverse effects that limit their use. To obtain localized and on-demand pharmacological action using light, we have designed photoisomerizable ligands based on azobenzene that mimic the tricyclic chemical structure and display reversibly controlled activity. Pseudo-analogues of the tricyclic antagonist pirenzepine demonstrate that this is an effective strategy in muscarinic acetylcholine receptors, showing stronger inhibition upon illumination both in vitro and in cardiac atria ex vivo. Despite the applied chemical modifications to make pirenzepine derivatives sensitive to light stimuli, the most potent candidate of the set, cryptozepine-2, maintained a moderate but promising M1 vs M2 subtype selectivity. These photoswitchable “crypto-azologs” of tricyclic drugs might open a general way to spatiotemporally target their therapeutic action while reducing their systemic toxicity and adverse effects. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 63 p.; application/pdf |
| اللغة: | English |
| تدمد: | 0022-2623 |
| العلاقة: | Versió postprint del document publicat a: https://doi.org/10.1021/acs.jmedchem.1c00504Test; Journal of Medicinal Chemistry, 2021, vol. 64, num.13, p. 9259-9270; https://doi.org/10.1021/acs.jmedchem.1c00504Test; http://hdl.handle.net/2445/178992Test |
| الإتاحة: | https://doi.org/10.1021/acs.jmedchem.1c00504Test http://hdl.handle.net/2445/178992Test |
| حقوق: | (c) American Chemical Society, 2021 ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.B9DAC1D2 |
| قاعدة البيانات: | BASE |
| تدمد: | 00222623 |
|---|