Synthesis and Biological Analysis of Iso-dimethyltryptamines in a Model of Light-Induced Retinal Degeneration

被引:1
作者
Pazur, Ethan J. [1 ]
Kalatanova, Anna [2 ]
Tasker, Nikhil R. [1 ]
Vainionpaa, Katri [2 ]
Leinonen, Henri [2 ]
Wipf, Peter [1 ,2 ]
机构
[1] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA
[2] Univ Eastern Finland, Sch Pharm, Yliopistonrinne 3, Kuopio 70211, Finland
来源
ACS MEDICINAL CHEMISTRY LETTERS | 2024年
基金
芬兰科学院;
关键词
Serotonin Receptor Agonists; 5-HTR; Ergot Alkaloids; Iso-dimethyltryptamines; LIRD; Ophthalmology; Retinal Diseases; MACULAR DEGENERATION; STARGARDT DISEASE; DAMAGE; MICE; SUSCEPTIBILITY; PHARMACOLOGY; RETINOPATHY; DISCOVERY; APOPTOSIS; COMPONENT;
D O I
10.1021/acsmedchemlett.4c00130
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Iso-dimethyltryptamine (isoDMT) analogues with heterocyclic substitutions at the indole C(3) were prepared in a hydrogen autotransfer alkylation and tested in combination with natural and unnatural clavine alkaloids in a model of light-induced retinal degeneration for protection against retinal degeneration. On the basis of measurements with optical coherence tomography and electroretinography, three compounds showed better efficacy than the positive control bromocriptine at equivalent systemically administered doses. These studies provide further insights into the role of serotonin receptors and their potential therapeutic applications in ocular diseases.
引用
收藏
页码:1049 / 1056
页数:8
相关论文
共 65 条
[1]   Suppression of Light-Induced Oxidative Stress in the Retina by Mitochondria-Targeted Antioxidant [J].
Baksheeva, Viktoriia E. ;
Tiulina, Veronika V. ;
Tikhomirova, Natalia K. ;
Gancharova, Olga S. ;
Komarov, Sergey V. ;
Philippov, Pavel P. ;
Zamyatnin, Andrey A., Jr. ;
Senin, Ivan I. ;
Zernii, Evgeni Yu. .
ANTIOXIDANTS, 2019, 8 (01)
[2]   A COMPARISON OF THE BEHAVIORAL-EFFECTS OF PROTEO-N AND DEUTERO-N, N-DIMETHYLTRYPTAMINE [J].
BEATON, JM ;
BARKER, SA ;
LIU, WF .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1982, 16 (05) :811-814
[3]   Buspirone Enhances Cell Survival and Preserves Structural Integrity during Oxidative Injury to the Retinal Pigment Epithelium [J].
Biswal, Manas R. ;
Paulson, Ryan J. ;
Vichare, Riddhi ;
Lewin, Alfred S. .
ANTIOXIDANTS, 2023, 12 (12)
[4]   Effect of ring fluorination on the pharmacology of hallucinogenic tryptamines [J].
Blair, JB ;
Kurrasch-Orbaugh, D ;
Marona-Lewicka, D ;
Cumbay, MG ;
Watts, VJ ;
Barker, EL ;
Nichols, DE .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (24) :4701-4710
[5]   cAMP and Photoreceptor Cell Death in Retinal Degeneration [J].
Charish, Jason .
RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY, 2019, 1185 :301-304
[6]   Synergistically acting agonists and antagonists of G protein-coupled receptors prevent photoreceptor cell degeneration [J].
Chen, Yu ;
Palczewska, Grazyna ;
Masuho, Ikuo ;
Gao, Songqi ;
Jin, Hui ;
Dong, Zhiqian ;
Gieser, Linn ;
Brooks, Matthew J. ;
Kiser, Philip D. ;
Kern, Timothy S. ;
Martemyanov, Kirill A. ;
Swaroop, Anand ;
Palczewski, Krzysztof .
SCIENCE SIGNALING, 2016, 9 (438)
[7]   Systems pharmacology identifies drug targets for Stargardt disease-associated retinal degeneration [J].
Chen, Yu ;
Palczewska, Grazyna ;
Mustafi, Debarshi ;
Golczak, Marcin ;
Dong, Zhiqian ;
Sawada, Osamu ;
Maeda, Tadao ;
Maeda, Akiko ;
Palczewski, Krzysztof .
JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (12) :5119-5134
[8]   Mechanism of All-trans-retinal Toxicity with Implications for Stargardt Disease and Age-related Macular Degeneration [J].
Chen, Yu ;
Okano, Kiichiro ;
Maeda, Tadao ;
Chauhan, Vishal ;
Golczak, Marcin ;
Maeda, Akiko ;
Palczewski, Krzysztof .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (07) :5059-5069
[9]   Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor [J].
Chistyakov, Dmitry, V ;
Baksheeva, Viktoriia E. ;
Tiulina, Veronika V. ;
Goriainov, Sergei, V ;
Azbukina, Nadezhda, V ;
Gancharova, Olga S. ;
Arifulin, Eugene A. ;
Komarov, Sergey, V ;
Chistyakov, Viktor V. ;
Tikhomirova, Natalia K. ;
Zamyatnin, Andrey A., Jr. ;
Philippov, Pavel P. ;
Senin, Ivan I. ;
Sergeeva, Marina G. ;
Zernii, Evgeni Yu .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (03)
[10]   Agonists at the Serotonin Receptor (5-HT1A) Protect the Retina from Severe Photo-Oxidative Stress [J].
Collier, Robert J. ;
Patel, Yamini ;
Martin, Elizabeth A. ;
Dembinska, Olga ;
Hellberg, Mark ;
Krueger, D. Scott ;
Kapin, Michael A. ;
Romano, Carmelo .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2011, 52 (05) :2118-2126