Indole Derivatives as Cyclooxygenase Inhibitors: Synthesis, Biological Evaluation and Docking Studies

Springer Science and Business Media LLC - Tập 23 Số 6 - Trang 1250
Muzamil Ahmad Bhat1, Mohamed A. Al‐Omar2, Mohammad Raish3, Mushtaq A. Ansari4, Hatem A. Abuelizz5, Ahmed H. Bakheit6,7, Ahmed M. Naglah8,9
1Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
2Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
3Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
4Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
5Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
6Department of Chemistry, Faculty of Science and Technology, El-Neelain University, P.O. Box 12702, Khartoum 11121, Sudan. [email protected].
7Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
8Department of Pharmaceutical Chemistry, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
9Peptide Chemistry Department, Chemical Industries Research Division, National Research, Centre, 12622-Dokki, Cairo, Egypt. [email protected].

Tóm tắt

A new series of 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N′-[(E)-(substituted phenyl) methylidene] acetohydrazide derivatives (S1–S18) were synthesized and evaluated for their anti-inflammatory activity, analgesic activity, ulcerogenic activity, lipid peroxidation, ulcer index and cyclooxygenase expression activities. All the synthesized compounds were in good agreement with spectral and elemental analysis. Three synthesized compounds (S3, S7 and S14) have shown significant anti-inflammatory activity as compared to the reference drug indomethacin. Compound S3 was further tested for ulcerogenic index and cyclooxygenase (COX) expression activity. It was selectively inhibiting COX-2 expression and providing the gastric sparing activity. Docking studies have revealed the potential of these compounds to bind with COX-2 enzyme. Compound S3 formed a hydrogen bond between OH of Tyr 355 and NH2 of Arg 120 with carbonyl group and this hydrogen bond was similar to that formed by indomethacin. This study provides insight for compound S3, as a new lead compound as anti-inflammatory agent and selective COX-2 inhibitor.

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