Bodipy‐Labeled Allopregnanolone: Synthesis, GABA A Receptor Positive Allosteric Modulation, In Silico Binding Pose Determination and Neurons Staining

Bodipy‐Labeled Allopregnanolone: Synthesis, GABA A Receptor Positive Allosteric Modulation, In Silico Binding Pose Determination and Neurons Staining Full article

Journal

Archiv der Pharmazie
ISSN: 0365-6233 , E-ISSN: 1521-4184

Output data

Year: 2026, Volume: 359, Number: 2, Article number : e70215, Pages count : 16 DOI: 10.1002/ardp.70215

Authors

Kolbaev Sergey N. ¹ , Uvarov Denis Y. ² , Smirnova Natalia ² , Vazetdinova Alina ^3,4 , Malomouzh Artem ^3,5 , Samigullin Dmitry ^3,5 , Goze Christine ⁶ , Denat Franck ⁶ , Zavarzin Igor V. ² , Sharonova Irina N. ¹ , Rossokhin Alexey V. ¹ , Volkova Yulia A. ²

Affiliations

1	Research Center of Neurology Moscow Russia
2	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences Moscow Russia
3	Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center, Russian Academy of Science Kazan Russia
4	Laboratory of Neurobiology, Kazan Federal University Kazan Russia
5	Department of Radiophotonics and Microwave Technologies Kazan National Research Technical University Named after A.N. Tupolev‐KAI Kazan Russia
6	Université Bourgogne Europe, CNRS, Institut de Chimie Moléculaire de l'Université de Bourgogne (ICMUB) Dijon France

The first BODIPY–allopregnanolone conjugates have been synthesized by selecting the C21 position for labeling. The steroidal moiety and BODIPY fluorophores were coupled through flexible amino acid-derived linkers, designed with rotatable bonds and a variable carbon chain length. Сonjugates were characterized, with quantum yields of up to 79% and high extinction coefficients. All compounds showed a reasonable ability to potentiate GABA-evoked currents in isolated cerebellar Purkinje neurons. Interactions of the conjugates with the GABAA receptor were investigated by molecular docking calculations, which predicted that the BODIPY fluorophore linked to 3α5αTHP via the C21 atom does not prevent the binding of the 3α5αTHP moiety at the neurosteroid site on the β(+)/α(−) intersubunit interfaces. Fluorescence microscopy studies demonstrated that the BODIPY-3α5αTHP III effectively stains Purkinje neurons in cerebellar slices and preferentially labels neuronal populations amidst coexisting astroglia in hippocampal tissue slices.

Kolbaev S.N. , Uvarov D.Y. , Smirnova N. , Vazetdinova A. , Malomouzh A. , Samigullin D. , Goze C. , Denat F. , Zavarzin I.V. , Sharonova I.N. , Rossokhin A.V. , Volkova Y.A.
Bodipy‐Labeled Allopregnanolone: Synthesis, GABA A Receptor Positive Allosteric Modulation, In Silico Binding Pose Determination and Neurons Staining
Archiv der Pharmazie. 2026. V.359. N2. e70215 :1-16. DOI: 10.1002/ardp.70215 WOS Scopus OpenAlex

Submitted:	Jul 2, 2025
Accepted:	Feb 13, 2026
Published online:	Mar 1, 2026

≡ Web of science:	WOS:001717078100014
≡ Scopus:	2-s2.0-105031428013
≡ OpenAlex:	W7133124854