Design, Synthesis and Biological Evaluation of Novel Quinazoline-Based Anti-inflammatory Agents Acting as PDE4B Inhibitors
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- Serya Rabah Ahmed Taha
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University
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- Abbas Abeer Hussin
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University
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- Ismail Nasser Saad Mohamed
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University
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- Esmat Ahmed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University
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- Abou El Ella Dalal Abdelrahman
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University
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Abstract
A novel series of quinzoline based compounds (IIIa–d, VIa–f, IXa–f) were designed, synthesized and screened for their inhibitory activity towards the PDE4B isoform. The in vivo anti-inflammatory effect of the titled compounds (IIIa–d, VIa–f, IXa–f) as well as their effect on the level of tumor necrosis factor (TNF-α) were evaluated. Among all of the synthesized compounds, IXb, IXd and IXf, exhibited good inhibitory activity against PDE4B enzyme with inhibition percentages of 42, 62 and 68%, respectively. Most of the tested compounds showed potent anti-inflammatory activity compared to indomethacin with a marked decrease in TNF-α level. The ulcerogenic effect of the tested compounds was also examined. The gastric mucosa of the tested animals remained intact after oral administration of the hit compounds. Additionally, docking study was used to explore the possible binding mode of the active compounds on the PDE4B enzyme as well as to illustrate the selectivity of the active hits on the PDE4B isoform.
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 63 (2), 102-116, 2015
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390282679154741760
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- NII Article ID
- 130004803769
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- NII Book ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL BIB ID
- 026069346
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- PubMed
- 25748781
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed