Abstract
The synthesis and anti-inflammatory effects of certain pyrazolo[4,3-c]quinoline derivatives 2a–2r are described. The anti-inflammatory activities of these derivatives were evaluated by means of inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among them, 3-amino-4-(4-hydroxyphenylamino)-1H-pyrazolo[4,3-c]-quinoline (2i) and 4-(3-amino-1H-pyrazolo[4,3-c]quinolin-4-ylamino)benzoic acid (2m) exhibited significant inhibition of LPS-stimulated NO production with a potency approximately equal to that of the positive control, 1400 W. Important structure features were analyzed by quantitative structure–activity relationship (QSAR) analysis to give better insights into the structure determinants for predicting the inhibitory effects on the accumulation of nitric oxide for RAW 264.7 cells in response to LPS. In addition, our results indicated that their anti-inflammatory effects involve the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expression. Further studies on the structural optimization are ongoing.
Highlights
Nitric oxide (NO), a gaseous free radical, is an important signaling molecule that is involved in a wide range of pathophysiological responses such as inflammation, carcinogenesis, and vasodilation [1,2,3]
Is essentially unregulated resulting in local tissue damage and many inflammatory diseases resulting in local tissue damage and many inflammatory diseases including rheumatoid arthritis, including rheumatoid arthritis, osteoarthritis, bowel disease andthe multiple osteoarthritis, inflammatory bowel disease andinflammatory multiple sclerosis
We have reported that furo[3,2:3,4]naphtha[1,2-d] imidazole derivatives represent a novel classa class ofofinhibitors of inducible nitric oxide synthase (iNOS)
Summary
Nitric oxide (NO), a gaseous free radical, is an important signaling molecule that is involved in a wide range of pathophysiological responses such as inflammation, carcinogenesis, and vasodilation [1,2,3]. Once expressed at high levels, and and smooth muscle cells [6]. Many efforts have been devoted to discovery the discovery of inhibitor of iNOS the past few[7,8,9,10,11,12,13]. Many efforts have been devoted to the of inhibitor of iNOS for thefor past few years [7,8,9,10,11,12,13]. Pyrazolo[4,3-c]quinolines has received recently received much attention ofnovel inhibitors iNOS [14]. Pyrazolo[4,3-c]quinolines has recently much attention for its for its anti-inflammatory, anti-cancer and β-glucuronidase inhibitory activities [15,16].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
