Computational modeling, docking, synthesis, characterization, and in vitro cyclooxygenase inhibitory activity of some novel non-steroidal anti-inflammatory prodrugs
Joint Authors
Amin, Dana Muhammad Hamad
Abd al-Hamid, Sarah Ramzi
Source
ZANCO Journal of Pure and Applied Sciences
Issue
Vol. 32, Issue 6 (31 Dec. 2020), pp.25-39, 15 p.
Publisher
Salahaddin University-Erbil Department of Scientific Publications
Publication Date
2020-12-31
Country of Publication
Iraq
No. of Pages
15
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Abstract EN
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed analgesic and anti-inflammatory drugs.
However, inhibition of cyclooxygenase1 and acidic groups such as carboxylic groups in most NSAIDs cause gastrointestinal (GI) side effects.
Therefore, masking the acidic groups till it pass through the GI tract will decrease the direct GI side effects and because N-(2,6-dimethylphenyl)-acetamide 1 also has anti-inflammatory activity so the synthesized ester prodrugs might act as mutual prodrugs.
2-Chloro-N-(2,6-dimethylphenyl)-acetamide 1 was utilized to synthesize ester prodrug of various NSAIDs 2a-e.
The 2- Chloro-N-(2,6-dimethylphenyl)-acetamide 1 undergo substitution reaction at α position with various sodium carboxylate of NSAIDs 2a-e in DMSO.
The constitution of the newly synthesized ester prodrugs of NSAIDs 3a-e had been confirmed depending on their IR, 1H and 13C-NMR spectral analysis.
The synthesized ester prodrugs 3a-e were screened for their in vitro inhibitory activities of COX-1 as well as COX-2 however, their COX inhibition activity increased compared with their starting 1 and 2a-e.
Physicochemical properties and ―Lipinski‘s rule of five‖ were assessed for compounds 3a-e, and they all satisfied the rule.
Furthermore molecular docking for compounds 3a-e into COX-1 and COX-2 was done, in which they showed binding free energies ΔGb in the range of (-8.9 to -9.8 kcal/mol) when docked into COX-1 and (-10.4 to -12.4 kcal/mol) into COX-2 enzymes.
American Psychological Association (APA)
Amin, Dana Muhammad Hamad& Abd al-Hamid, Sarah Ramzi. 2020. Computational modeling, docking, synthesis, characterization, and in vitro cyclooxygenase inhibitory activity of some novel non-steroidal anti-inflammatory prodrugs. ZANCO Journal of Pure and Applied Sciences،Vol. 32, no. 6, pp.25-39.
https://search.emarefa.net/detail/BIM-1384603
Modern Language Association (MLA)
Amin, Dana Muhammad Hamad& Abd al-Hamid, Sarah Ramzi. Computational modeling, docking, synthesis, characterization, and in vitro cyclooxygenase inhibitory activity of some novel non-steroidal anti-inflammatory prodrugs. ZANCO Journal of Pure and Applied Sciences Vol. 32, no. 6 (2020), pp.25-39.
https://search.emarefa.net/detail/BIM-1384603
American Medical Association (AMA)
Amin, Dana Muhammad Hamad& Abd al-Hamid, Sarah Ramzi. Computational modeling, docking, synthesis, characterization, and in vitro cyclooxygenase inhibitory activity of some novel non-steroidal anti-inflammatory prodrugs. ZANCO Journal of Pure and Applied Sciences. 2020. Vol. 32, no. 6, pp.25-39.
https://search.emarefa.net/detail/BIM-1384603
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references : p. 37-39
Record ID
BIM-1384603