Synthesis of some new amide-linked bipyrazoles and their evaluation as anti-inflammatory and analgesic agents.
Four series of new bipyrazoles comprising the N-phenylpyrazole scaffold linked to polysubstituted pyrazoles or to antipyrine moiety through different amide linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory and analgesic activities. In vitro COX-1/COX-2 inhibition study revealed that compound 16b possessed the lowest IC50 value against both COX-1 and COX-2. Moreover, the effect of the most promising compounds on inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) protein expression in lipopolysaccharide (LPS)-activated rat monocytes was also investigated. The results revealed that some of the synthesized compounds showed anti-inflammatory and/or analgesic activity with less ulcerogenic potential than the reference drug diclofenac sodium and are well tolerated by experimental animals. Moreover, they significantly inhibited iNOS and COX-2 protein expression induced by LPS stimulation. Compounds 16b and 18 were proved to display anti-inflammatory activity superior to diclofenac sodium and analgesic activity equivalent to it with minimal ulcerogenic potential.
a School of Medicine, Lebanese American University , Byblos , Lebanon .
Wissam H
WH
Faour
b Department of Pharmaceutical Sciences , School of Pharmacy, Lebanese American University , Byblos , Lebanon .
Mohamed
M
Mroueh
c Department of Natural Sciences , School of Arts and Sciences, Lebanese American University , Byblos , Lebanon .
Costatantine F
CF
Daher
d Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Alexandria University , Alexandria , Egypt .|e Department of Analytical & Pharmaceutical Chemistry , Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria , Alexandria , Egypt .
Rasha Y
RY
Elbayaa
d Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Alexandria University , Alexandria , Egypt .
Hanan M
HM
Ragab
f Department of Pharmacology and Therapeutics , Faculty of Pharmacy, Beirut Arab University , Beirut , Lebanon .|g Department of Pharmacology and Toxicology , Faculty of Pharmacy, Damanhour University , Damanhour , Egypt , and.
Asser I
AI
Ghoneim
h Department of Pharmacology , Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria , Alexandria , Egypt.
Ahmed I
AI
El-Mallah
d Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Alexandria University , Alexandria , Egypt .
Hayam M A
HM
Ashour
D000577:Amides / Q000737:chemistry*; D000700:Analgesics / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D011720:Pyrazoles / Q000737:chemistry*; D013057:Spectrum Analysis / Q000379:methods
D000577:Amides; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D011720:Pyrazoles
Anti-inflammatory; COX-2; analgesic; iNOS