E/Z Isomerism of the Potential Antiepileptic Drug GIZH-298
The synthesis, purification, and comprehensive characterization of the E- and Z-isomers of the prospective anticonvulsant compound GIZH-298 were carried out. It was demonstrated that both isomers could be obtained in a pure form by isolating the corresponding oximes at the initial stage of synthesis. The E- and Z-isomers exhibit pronounced differences in their physicochemical characteristics, spectral features, and pharmacological profiles. Z-GIZH-298 was found to be photosensitive, undergoing Z-E isomerization upon irradiation, as confirmed by both theoretical analysis and experimental observations. Additionally, partial conversion to the E-form occurs during prolonged reflux of Z-GIZH-298 in polar solvents, whereas the compound remains stable in aqueous and acidic media at ambient temperature. In the maximal electroshock assay, both isomers demonstrated anticonvulsant activity, with Z-GIZH-298 showing substantially higher efficacy than its E-counterpart. These findings highlight the need to account for potential E-isomer formation when considering further development of Z-GIZH-298 as a promising anticonvulsant agent.
Authors
- Timofey V. Losev (ORCID: https://orcid.org/0000-0001-8699-4736)
- Michael G. Medvedev (ORCID: https://orcid.org/0000-0001-7070-4052)
- Sergey V. Shorunov
- А. Д. Дурнев (ORCID: https://orcid.org/0000-0003-0912-7684)
- Г. В. Мокров (ORCID: https://orcid.org/0000-0003-2617-0334)
- V. E. Biryukova (ORCID: https://orcid.org/0009-0000-9586-6971)
- Svetlana A. Litvinova
- A. G. Rebeko
- Tatiana Yu. Vorobyova
- Liubov N. Grushevskaya (ORCID: https://orcid.org/0000-0002-3794-9661)
- Konstantin A. Lyssenko (ORCID: https://orcid.org/0000-0002-3500-1287)
- Oxana Yu. Kravtsova
- Ekaterina A. Nikitina
- Tatiana A. Voronina
- Aliy K. Zhanataev (ORCID: https://orcid.org/0000-0002-7673-8672)
- Marat M. Islamov
- Natalia A. Gladysheva
- Dmitry N. Kuznetsov
- Ksenia M. Malashkeevich
- Vladimir L. Dorofeev (ORCID: https://orcid.org/0009-0004-3584-3742)
- Maria S. Sergeeva (ORCID: https://orcid.org/0000-0002-7155-6714)
Institutions
- Lomonosov Moscow State University (RU)
- N.D. Zelinsky Institute of Organic Chemistry (RU)
- All-Russian State Scientific Research Institute for Control, Standardization and Certification of Veterinary Preparations (RU)
- Medical Technologies (Czechia) (CZ)
Publication Details
- Journal
- Molecules
- Published
- 2026-05-29
- DOI
- https://doi.org/10.3390/molecules31111872
- Primary Topic
- Radical Photochemical Reactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministry of Education and Science of the Russian Federation