2. Academic Validation
  3. Neurotropic Effects In Vivo of New Tryptamino-Triazines Compared to GABA Effectors

Neurotropic Effects In Vivo of New Tryptamino-Triazines Compared to GABA Effectors

  • ACS Chem Neurosci. 2025 Dec 17;16(24):4769-4782. doi: 10.1021/acschemneuro.5c00884.
Anatoly Demchenko 1 2 3,  Artur Martynov 4,  Yevhenii Novodvorskyi 5,  Oleh Yadlovskyi 3,  Oleh Moskalenko 2,  Tatyana Bomko 4,  Tatyana Nosalsky 4,  Sergii Demchenko 6,  Sergiy Yarmoluk 6
Affiliations

Affiliations

  • 1 Department of Chemistry, Pontifical Catholic University of Rio de Janeiro (PUC-Rio), 225-Marquês de São Vicente St., Rio de Janeiro 22451-900, Rio de Janeiro Brazil.
  • 2 Department of Chemistry and Pharmacy, Nizhyn Mykola Gogol State University, 2-Hrafska St., Nizhyn, Chernihivs'ka Oblast 16600, Ukraine.
  • 3 Institute of Pharmacology and Toxicology, National Academy of Medical Sciences, 14-Anton Tsedik St., Kyiv 03057, Ukraine.
  • 4 Mechnikov Institute of Microbiology and Immunology of the National Academy of Medical Sciences of Ukraine, 14/16 -G. Skovorody St., Kharkiv 61057, Ukraine.
  • 5 ChemBiocenter, Kyiv National Taras Shevchenko University, 61-Winston Churchill St., Kyiv 02094, Ukraine.
  • 6 Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, 150-Zabolotnogo Str., Kyiv 03143, Ukraine.
PMID: 41343685 DOI: 10.1021/acschemneuro.5c00884
Abstract

Anxiety and Other neurotic disorders are significant medical and social issues, affecting 10-20% of people in developed countries, with an annual increase of over 10%. These conditions are becoming a greater concern due to treatment costs, missed work, decreased productivity, and their impact on relationships and socialization. As a result, developing effective treatments for neurotic disorders is a key goal in medicine and pharmacology. For the first time, we synthesized derivatives containing both tryptamine and triazine fragments and demonstrated their neurotropic activity, in particular their anxiolytic effect. When examining their binding using the docking method (Autodock Vina multiligand) to the GABAa receptor (PDB ID: 6X3X) and GABA-AT (PDB ID: 1SF2), compounds 4-11a-i showed minimal binding energies. In animal studies, compounds 9b and 11g demonstrated notable antianxiety effects, influencing behaviors such as approach to the arena center, grooming, and bolus count. Compound 11g 6-(4-chlorobenzyl)-3-[2-(6-methoxy-1H-indol-3-yl)-ethylamino]-4H-[1,2,4]triazin-5-one had the lowest IC50 value at 19.8 ± 0.62, indicating high potency, and appeared to function similarly to diazepam without impairing normal exploration or movement. Notably, 9b outperformed Other tested drugs. Its derivative 11g displayed the lowest energy binding with GABAA receptor and GABA-AT, which likely accounts for its high activity.

Keywords

13C NMR; 1H NMR; Autodock Vina docking in silico; antianxiety in vivo; open field study; organic synthesis; tryptamino-triazines.

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