TY - JOUR
T1 - Discovery of potential anti-inflammatory drugs
T2 - Diaryl-1,2,4-triazoles bearing N-hydroxyurea moiety as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase
AU - Jiang, Bo
AU - Huang, Xiaojing
AU - Yao, Hequan
AU - Jiang, Jieyun
AU - Wu, Xiaoming
AU - Jiang, Siyi
AU - Wang, Qiujuan
AU - Lu, Tao
AU - Xu, Jinyi
PY - 2014/4/7
Y1 - 2014/4/7
N2 - A series of hybrids from diaryl-1,2,4-triazole and hydroxamic acid or N-hydroxyurea were synthesized and evaluated as novel anti-inflammatory agents. The biological data showed that (i) all the compounds showed dual COX-2/5-LOX inhibitory activities in vitro, and 15e showed optimal inhibitory activities (COX-2: IC50 = 0.15 μM, 5-LOX: IC50 = 0.85 μM), (ii) 15e selectively inhibited COX-2 relative to COX-1 with selectivity index (SI = 0.012) comparable to celecoxib (SI = 0.015), (iii) 15e exhibited potent anti-inflammatory activity (inhibition: 54.1%) which was comparable to the reference drug celecoxib (inhibition: 46.7%) in a xylene-induced ear edema assay, and (iv) 15e displayed promising analgesic activity in acetic acid-induced writhing response and hot-plate assay. Finally, a molecular modeling study revealed the binding interactions of 15e with COX-2 and 5-LOX. Our findings suggest that 15e may be a promising anti-inflammatory agent for further evaluation.
AB - A series of hybrids from diaryl-1,2,4-triazole and hydroxamic acid or N-hydroxyurea were synthesized and evaluated as novel anti-inflammatory agents. The biological data showed that (i) all the compounds showed dual COX-2/5-LOX inhibitory activities in vitro, and 15e showed optimal inhibitory activities (COX-2: IC50 = 0.15 μM, 5-LOX: IC50 = 0.85 μM), (ii) 15e selectively inhibited COX-2 relative to COX-1 with selectivity index (SI = 0.012) comparable to celecoxib (SI = 0.015), (iii) 15e exhibited potent anti-inflammatory activity (inhibition: 54.1%) which was comparable to the reference drug celecoxib (inhibition: 46.7%) in a xylene-induced ear edema assay, and (iv) 15e displayed promising analgesic activity in acetic acid-induced writhing response and hot-plate assay. Finally, a molecular modeling study revealed the binding interactions of 15e with COX-2 and 5-LOX. Our findings suggest that 15e may be a promising anti-inflammatory agent for further evaluation.
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U2 - 10.1039/c3ob41936c
DO - 10.1039/c3ob41936c
M3 - Article
C2 - 24562695
AN - SCOPUS:84897712532
SN - 1477-0520
VL - 12
SP - 2114
EP - 2127
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 13
ER -