Novel sulindac derivatives: synthesis, characterisation, evaluation of antioxidant, analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibition activity
A new series of N′-(substituted phenyl)-2-(1-(4-(methylsulfinyl) benzylidene)−5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide derivatives (1 – 25) were prepared in good yields in an efficient manner. All the compounds were fully characterised by the elemental analysis and spectral data. Synthesised...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | http://dx.doi.org/10.1080/14756366.2020.1746783 |
| _version_ | 1818649123042099200 |
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| author | Mashooq A. Bhat Mohamed A. Al-Omar Nawaf A. Alsaif Abdulrahman A. Almehizia Ahmed M. Naglah Suhail Razak Azmat Ali Khan Naeem Mahmood Ashraf |
| author_facet | Mashooq A. Bhat Mohamed A. Al-Omar Nawaf A. Alsaif Abdulrahman A. Almehizia Ahmed M. Naglah Suhail Razak Azmat Ali Khan Naeem Mahmood Ashraf |
| author_sort | Mashooq A. Bhat |
| collection | DOAJ |
| description | A new series of N′-(substituted phenyl)-2-(1-(4-(methylsulfinyl) benzylidene)−5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide derivatives (1 – 25) were prepared in good yields in an efficient manner. All the compounds were fully characterised by the elemental analysis and spectral data. Synthesised compounds were evaluated for antioxidant activity by DPPH method. Compounds 7 (R = 3-methoxyphenyl), 3 (R = 4-dimethylaminophenyl) and 23 (R = 2,4,5-trimethoxy phenyl) substitutions were found to be having highly potent antioxidant activity. Compound 3, with para dimethylaminophenyl substitution was found to be having highest antioxidant activity. It was further evaluated in vivo for various analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibitory activity in different animal models. Lead compound 3 was found to be significant anti-inflammatory and analgesic agent. It was also evaluated for ulcerogenic activity and demonstrated significant ulcerogenic reduction activity in ethanol and indomethacin model. The LD50 of compound 3 was found to be 131 mg/kg. The animals treated with compound 3 prior to cisplatin treatment resulted in a significant reduction in COX-2 protein expression when compared to cisplatin-treated group. Sulindac derivative with para dimethylaminophenyl substitution was found to be the most potent antioxidant, anti-inflammatory and analgesic agent as well as with significant gastric sparing activity as compared to standard drug sulindac. Compound 3 significantly downregulated liver tissue COX‐2 gene expression. |
| first_indexed | 2024-12-17T01:29:19Z |
| format | Article |
| id | doaj.art-fc48ed72e9114ccfac79c9f55bf0f370 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-17T01:29:19Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-fc48ed72e9114ccfac79c9f55bf0f3702022-12-21T22:08:37ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742020-01-0135192193410.1080/14756366.2020.17467831746783Novel sulindac derivatives: synthesis, characterisation, evaluation of antioxidant, analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibition activityMashooq A. Bhat0Mohamed A. Al-Omar1Nawaf A. Alsaif2Abdulrahman A. Almehizia3Ahmed M. Naglah4Suhail Razak5Azmat Ali Khan6Naeem Mahmood Ashraf7Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud UniversityDepartment of Community Health Sciences, College of Applied Medical Sciences, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Biochemistry and Biotechnology, The University of GujratA new series of N′-(substituted phenyl)-2-(1-(4-(methylsulfinyl) benzylidene)−5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide derivatives (1 – 25) were prepared in good yields in an efficient manner. All the compounds were fully characterised by the elemental analysis and spectral data. Synthesised compounds were evaluated for antioxidant activity by DPPH method. Compounds 7 (R = 3-methoxyphenyl), 3 (R = 4-dimethylaminophenyl) and 23 (R = 2,4,5-trimethoxy phenyl) substitutions were found to be having highly potent antioxidant activity. Compound 3, with para dimethylaminophenyl substitution was found to be having highest antioxidant activity. It was further evaluated in vivo for various analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibitory activity in different animal models. Lead compound 3 was found to be significant anti-inflammatory and analgesic agent. It was also evaluated for ulcerogenic activity and demonstrated significant ulcerogenic reduction activity in ethanol and indomethacin model. The LD50 of compound 3 was found to be 131 mg/kg. The animals treated with compound 3 prior to cisplatin treatment resulted in a significant reduction in COX-2 protein expression when compared to cisplatin-treated group. Sulindac derivative with para dimethylaminophenyl substitution was found to be the most potent antioxidant, anti-inflammatory and analgesic agent as well as with significant gastric sparing activity as compared to standard drug sulindac. Compound 3 significantly downregulated liver tissue COX‐2 gene expression.http://dx.doi.org/10.1080/14756366.2020.1746783sulindac hydrazidehydrazonesantioxidantanalgesicanti-inflammatorycox-2 activity |
| spellingShingle | Mashooq A. Bhat Mohamed A. Al-Omar Nawaf A. Alsaif Abdulrahman A. Almehizia Ahmed M. Naglah Suhail Razak Azmat Ali Khan Naeem Mahmood Ashraf Novel sulindac derivatives: synthesis, characterisation, evaluation of antioxidant, analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibition activity Journal of Enzyme Inhibition and Medicinal Chemistry sulindac hydrazide hydrazones antioxidant analgesic anti-inflammatory cox-2 activity |
| title | Novel sulindac derivatives: synthesis, characterisation, evaluation of antioxidant, analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibition activity |
| title_full | Novel sulindac derivatives: synthesis, characterisation, evaluation of antioxidant, analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibition activity |
| title_fullStr | Novel sulindac derivatives: synthesis, characterisation, evaluation of antioxidant, analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibition activity |
| title_full_unstemmed | Novel sulindac derivatives: synthesis, characterisation, evaluation of antioxidant, analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibition activity |
| title_short | Novel sulindac derivatives: synthesis, characterisation, evaluation of antioxidant, analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibition activity |
| title_sort | novel sulindac derivatives synthesis characterisation evaluation of antioxidant analgesic anti inflammatory ulcerogenic and cox 2 inhibition activity |
| topic | sulindac hydrazide hydrazones antioxidant analgesic anti-inflammatory cox-2 activity |
| url | http://dx.doi.org/10.1080/14756366.2020.1746783 |
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