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Design, Synthesis and Pharmacological Evaluation of Novel C(2),C(3)-Quinoxaline Derivatives as Promising Anxiolytic Agents
A new series of quinoxaline derivatives, 2a–4b, were synthesized and their anxiolytic potential was evaluated in vivo using elevated plus maze (EPM), open field (OF) and light-dark box (LDB) techniques. According to the results of the EPM, four active compounds were found in 2a, 2b, 2c, 4b. Their an...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696749/ https://www.ncbi.nlm.nih.gov/pubmed/36430878 http://dx.doi.org/10.3390/ijms232214401 |
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author | Maltsev, Dmitriy V. Skripka, Maria O. Spasov, Alexander A. Vassiliev, Pavel M. Perfiliev, Maxim A. Divaeva, Lyudmila N. Zubenko, Alexander A. Morkovnik, Anatolii S. Klimenko, Alexander I. Miroshnikov, Mikhail V. Klochkov, Vladlen G. Ianalieva, Laura R. |
author_facet | Maltsev, Dmitriy V. Skripka, Maria O. Spasov, Alexander A. Vassiliev, Pavel M. Perfiliev, Maxim A. Divaeva, Lyudmila N. Zubenko, Alexander A. Morkovnik, Anatolii S. Klimenko, Alexander I. Miroshnikov, Mikhail V. Klochkov, Vladlen G. Ianalieva, Laura R. |
author_sort | Maltsev, Dmitriy V. |
collection | PubMed |
description | A new series of quinoxaline derivatives, 2a–4b, were synthesized and their anxiolytic potential was evaluated in vivo using elevated plus maze (EPM), open field (OF) and light-dark box (LDB) techniques. According to the results of the EPM, four active compounds were found in 2a, 2b, 2c, 4b. Their anxiolytic properties were confirmed in terms of LDB and the most active was compound 2b. In the OF, only 2c had an influence on the locomotor activity of the rodents. Thus, the most promising substance was determined; this was 2b, which has the structure of 2-(2-{[3-(4-tert-butylphenyl)quinoxaline-2-yl]methyl}-4,5-dimethoxyphenyl)-N-methylethan-1-amine hydrochloride. The obtained data were analyzed with the pharmacophore feature prediction approach, which made it possible to compare the structures of the studied compounds with the reference drug diazepam, and to determine the contribution of pharmacophores to the manifestation of the activity under study. ADMET analysis was carried out for compound 2b and the acute oral toxicity of this substance was also tested in vivo. As a result of the study, a promising compound with a high anxiolytic effect and low level of toxicity 2b was found, which is of interest for further preclinical study of its properties. |
format | Online Article Text |
id | pubmed-9696749 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96967492022-11-26 Design, Synthesis and Pharmacological Evaluation of Novel C(2),C(3)-Quinoxaline Derivatives as Promising Anxiolytic Agents Maltsev, Dmitriy V. Skripka, Maria O. Spasov, Alexander A. Vassiliev, Pavel M. Perfiliev, Maxim A. Divaeva, Lyudmila N. Zubenko, Alexander A. Morkovnik, Anatolii S. Klimenko, Alexander I. Miroshnikov, Mikhail V. Klochkov, Vladlen G. Ianalieva, Laura R. Int J Mol Sci Article A new series of quinoxaline derivatives, 2a–4b, were synthesized and their anxiolytic potential was evaluated in vivo using elevated plus maze (EPM), open field (OF) and light-dark box (LDB) techniques. According to the results of the EPM, four active compounds were found in 2a, 2b, 2c, 4b. Their anxiolytic properties were confirmed in terms of LDB and the most active was compound 2b. In the OF, only 2c had an influence on the locomotor activity of the rodents. Thus, the most promising substance was determined; this was 2b, which has the structure of 2-(2-{[3-(4-tert-butylphenyl)quinoxaline-2-yl]methyl}-4,5-dimethoxyphenyl)-N-methylethan-1-amine hydrochloride. The obtained data were analyzed with the pharmacophore feature prediction approach, which made it possible to compare the structures of the studied compounds with the reference drug diazepam, and to determine the contribution of pharmacophores to the manifestation of the activity under study. ADMET analysis was carried out for compound 2b and the acute oral toxicity of this substance was also tested in vivo. As a result of the study, a promising compound with a high anxiolytic effect and low level of toxicity 2b was found, which is of interest for further preclinical study of its properties. MDPI 2022-11-19 /pmc/articles/PMC9696749/ /pubmed/36430878 http://dx.doi.org/10.3390/ijms232214401 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Maltsev, Dmitriy V. Skripka, Maria O. Spasov, Alexander A. Vassiliev, Pavel M. Perfiliev, Maxim A. Divaeva, Lyudmila N. Zubenko, Alexander A. Morkovnik, Anatolii S. Klimenko, Alexander I. Miroshnikov, Mikhail V. Klochkov, Vladlen G. Ianalieva, Laura R. Design, Synthesis and Pharmacological Evaluation of Novel C(2),C(3)-Quinoxaline Derivatives as Promising Anxiolytic Agents |
title | Design, Synthesis and Pharmacological Evaluation of Novel C(2),C(3)-Quinoxaline Derivatives as Promising Anxiolytic Agents |
title_full | Design, Synthesis and Pharmacological Evaluation of Novel C(2),C(3)-Quinoxaline Derivatives as Promising Anxiolytic Agents |
title_fullStr | Design, Synthesis and Pharmacological Evaluation of Novel C(2),C(3)-Quinoxaline Derivatives as Promising Anxiolytic Agents |
title_full_unstemmed | Design, Synthesis and Pharmacological Evaluation of Novel C(2),C(3)-Quinoxaline Derivatives as Promising Anxiolytic Agents |
title_short | Design, Synthesis and Pharmacological Evaluation of Novel C(2),C(3)-Quinoxaline Derivatives as Promising Anxiolytic Agents |
title_sort | design, synthesis and pharmacological evaluation of novel c(2),c(3)-quinoxaline derivatives as promising anxiolytic agents |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696749/ https://www.ncbi.nlm.nih.gov/pubmed/36430878 http://dx.doi.org/10.3390/ijms232214401 |
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