Fused Triazole-Azepine Hybrids as Potential Non-Steroidal Antiinflammatory Agents
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the oldest and most widely used groups of drugs nowadays. However, the problem of searching for and creating new NSAIDs remains open, primarily due to the risks owing to their short- and long-term use. In this context, triazole-azepine hybrid...
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MDPI AG
2023-05-01
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| Series: | Scientia Pharmaceutica |
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| Online Access: | https://www.mdpi.com/2218-0532/91/2/26 |
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| author | Sergii Demchenko Roman Lesyk Oleh Yadlovskyi Serhii Holota Sergii Yarmoluk Sergii Tsyhankov Anatolii Demchenko |
| author_facet | Sergii Demchenko Roman Lesyk Oleh Yadlovskyi Serhii Holota Sergii Yarmoluk Sergii Tsyhankov Anatolii Demchenko |
| author_sort | Sergii Demchenko |
| collection | DOAJ |
| description | Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the oldest and most widely used groups of drugs nowadays. However, the problem of searching for and creating new NSAIDs remains open, primarily due to the risks owing to their short- and long-term use. In this context, triazole-azepine hybrid molecules are attractive and prospective objects for the rational design of novel potential NSAIDs. In the present work studies of 3-aryl-6,7,8,9-tetrahydro-5<i>H</i>-[1,2,4]triazolo[4,3-<i>a</i>]azepines as potential non-steroidal anti-inflammatory agents are reported. Evaluation of drug-like properties for all tested triazole-azepine hybrids was performed in silico using SwissADME. The screening of analgesic and anti-inflammatory activities was performed in vivo using acid-induced writhing and carrageenin-induced hind paw oedema models in mice. Derivatives with activity levels more potent compared with reference drugs ketorolac and diclofenac sodium were identified. Preliminary SAR was performed based on the screening results. |
| first_indexed | 2024-03-11T01:58:26Z |
| format | Article |
| id | doaj.art-de0e65fb6f5d4433b373535ffadc93db |
| institution | Directory Open Access Journal |
| issn | 0036-8709 2218-0532 |
| language | English |
| last_indexed | 2024-03-11T01:58:26Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Scientia Pharmaceutica |
| spelling | doaj.art-de0e65fb6f5d4433b373535ffadc93db2023-11-18T12:29:47ZengMDPI AGScientia Pharmaceutica0036-87092218-05322023-05-019122610.3390/scipharm91020026Fused Triazole-Azepine Hybrids as Potential Non-Steroidal Antiinflammatory AgentsSergii Demchenko0Roman Lesyk1Oleh Yadlovskyi2Serhii Holota3Sergii Yarmoluk4Sergii Tsyhankov5Anatolii Demchenko6Institute of Molecular Biology and Genetics of NASU, Zabolotnogo Str. 150, 03143 Kyiv, UkraineDepartment of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, UkraineInstitute of Pharmacology and Toxicology, Anton Tsedik 14, 03057 Kiev, UkraineDepartment of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, UkraineInstitute of Molecular Biology and Genetics of NASU, Zabolotnogo Str. 150, 03143 Kyiv, UkraineDepartment of Chemistry and Pharmacy, Nizhyn Mykola Gogol State University, 16600 Nizhyn, UkraineDepartment of Chemistry and Pharmacy, Nizhyn Mykola Gogol State University, 16600 Nizhyn, UkraineNon-steroidal anti-inflammatory drugs (NSAIDs) are one of the oldest and most widely used groups of drugs nowadays. However, the problem of searching for and creating new NSAIDs remains open, primarily due to the risks owing to their short- and long-term use. In this context, triazole-azepine hybrid molecules are attractive and prospective objects for the rational design of novel potential NSAIDs. In the present work studies of 3-aryl-6,7,8,9-tetrahydro-5<i>H</i>-[1,2,4]triazolo[4,3-<i>a</i>]azepines as potential non-steroidal anti-inflammatory agents are reported. Evaluation of drug-like properties for all tested triazole-azepine hybrids was performed in silico using SwissADME. The screening of analgesic and anti-inflammatory activities was performed in vivo using acid-induced writhing and carrageenin-induced hind paw oedema models in mice. Derivatives with activity levels more potent compared with reference drugs ketorolac and diclofenac sodium were identified. Preliminary SAR was performed based on the screening results.https://www.mdpi.com/2218-0532/91/2/26NSAIDstriazoleazepinehybrid moleculesanalgesic activityanti-inflammatory activity |
| spellingShingle | Sergii Demchenko Roman Lesyk Oleh Yadlovskyi Serhii Holota Sergii Yarmoluk Sergii Tsyhankov Anatolii Demchenko Fused Triazole-Azepine Hybrids as Potential Non-Steroidal Antiinflammatory Agents Scientia Pharmaceutica NSAIDs triazole azepine hybrid molecules analgesic activity anti-inflammatory activity |
| title | Fused Triazole-Azepine Hybrids as Potential Non-Steroidal Antiinflammatory Agents |
| title_full | Fused Triazole-Azepine Hybrids as Potential Non-Steroidal Antiinflammatory Agents |
| title_fullStr | Fused Triazole-Azepine Hybrids as Potential Non-Steroidal Antiinflammatory Agents |
| title_full_unstemmed | Fused Triazole-Azepine Hybrids as Potential Non-Steroidal Antiinflammatory Agents |
| title_short | Fused Triazole-Azepine Hybrids as Potential Non-Steroidal Antiinflammatory Agents |
| title_sort | fused triazole azepine hybrids as potential non steroidal antiinflammatory agents |
| topic | NSAIDs triazole azepine hybrid molecules analgesic activity anti-inflammatory activity |
| url | https://www.mdpi.com/2218-0532/91/2/26 |
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