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

作者：Naglah, Ahmed M^*; Ahmed, Atallah F^*; Wen, Zhi Hong; Al Omar, Mohamed A; Amr, Abd El Galil E; Kalmouch, Atef

来源：Molecules, 2016, 21(4): 498.

DOI：10.3390/molecules21040498

• nalidixic acid
• isatin
• L-amino acid
• Schiff base
• iNOS
• COX-2
• anti-inflammatory
• microwave irradiation

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 mu M). 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.

• 出版日期2016-4
• 单位中山大学