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Molecules 2016, 21(4), 498; doi:10.3390/molecules21040498

New Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Inhibitors, Nalidixic Acid Linked to Isatin Schiff Bases via Certain l-Amino Acid Bridges

1
Department of Pharmaceutical Chemistry, Drug Exploration & Development Chair, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
2
Peptide Chemistry Department, National Research Centre, 12622-Dokki, Cairo 12311, Egypt
3
Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
4
Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
5
Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan
6
Applied Organic Chemistry Department, National Research Centre, 12622-Dokki, Cairo 12311, Egypt
*
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 21 February 2016 / Revised: 2 April 2016 / Accepted: 12 April 2016 / Published: 15 April 2016
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [928 KB, uploaded 20 April 2016]   |  

Abstract

A series of new Schiff bases were synthesized by condensation of isatins with the nalidixic acid-l-amino acid hydrazides. Prior to hydrazide formation, a peptide linkage has been prepared via coupling of nalidixic acid with appropriate l-amino acid methyl esters to yield 3a–c. The chemical structures of the new Schiff bases (5b and 5d–h) were confirmed by means of IR, NMR, mass spectroscopic, and elemental analyses. The anti-inflammatory activity of these Schiff bases was evaluated via measurement of the expressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells model. The Schiff bases exhibited significant dual inhibitory effect against the induction of the pro-inflammatory iNOS and COX-2 proteins with variable potencies. However, they strongly down-regulated the iNOS expression to the level of 16.5% ± 7.4%–42.2% ± 19.6% compared to the effect on COX-2 expression (<56.4% ± 3.1% inhibition) at the same concentration (10 μM). The higher iNOS inhibition activity of the tested Schiff bases, relative to that of COX-2, seems to be a reflection of the combined suppressive effects exerted by their nalidixic acid, isatins (4a–c), and l-amino acid moieties against iNOS expression. These synthesized nalidixic acid-l-amino acid-isatin conjugates can be regarded as a novel class of anti-inflammatory antibacterial agents. View Full-Text
Keywords: nalidixic acid; isatin; l-amino acid; Schiff base; iNOS; COX-2; anti-inflammatory; microwave irradiation nalidixic acid; isatin; l-amino acid; Schiff base; iNOS; COX-2; anti-inflammatory; microwave irradiation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Naglah, A.M.; Ahmed, A.F.; Wen, Z.-H.; Al-Omar, M.A.; Amr, A.E.-G.; Kalmouch, A. New Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Inhibitors, Nalidixic Acid Linked to Isatin Schiff Bases via Certain l-Amino Acid Bridges. Molecules 2016, 21, 498.

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