TY - JOUR
T1 - Design, synthesis, anti-inflammatory activity and molecular docking of potential novel antipyrine and pyrazolone analogs as cyclooxygenase enzyme (COX) inhibitors
AU - El Sayed, Mardia T.
AU - El-Sharief, Marwa A.M.Sh
AU - Zarie, Eman S.
AU - Morsy, Nesrin M.
AU - Elsheakh, Ahmed R.
AU - Voronkov, Andrey
AU - Berishvili, Vladimir
AU - Hassan, Ghada S.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - As a part of a directed program for development of new active agents, novel heterocyclic derivatives with antipyrine and pyrazolone moieties -incorporated in- have been designed and synthesized. Starting with 4-arylidene-3-methyl-1-phenyl-5-pyrazolone derivative 2a,b novel Mannich bases derivatives have been synthesized and biologically evaluated for their anti-inflammatory activity. Furthermore, the activity of such compounds has been tested interestingly as COX-1 and COX-2 inhibitors. Structure elucidation of the synthesized compounds was attained by the use of elemental analysis, IR, 1H NMR, 13C NMR, and Mass spectrometry techniques. Compounds 3b, 3d and 4b represent the high % inhibition values for both COX-1 and COX-2. On the other hand, compound 8 showed little selectivity against COX-2 while compound 10 showed good selectivity against COX-1 only. Structure activity relationship has been discussed and the results were confirmed by molecular docking calculations.
AB - As a part of a directed program for development of new active agents, novel heterocyclic derivatives with antipyrine and pyrazolone moieties -incorporated in- have been designed and synthesized. Starting with 4-arylidene-3-methyl-1-phenyl-5-pyrazolone derivative 2a,b novel Mannich bases derivatives have been synthesized and biologically evaluated for their anti-inflammatory activity. Furthermore, the activity of such compounds has been tested interestingly as COX-1 and COX-2 inhibitors. Structure elucidation of the synthesized compounds was attained by the use of elemental analysis, IR, 1H NMR, 13C NMR, and Mass spectrometry techniques. Compounds 3b, 3d and 4b represent the high % inhibition values for both COX-1 and COX-2. On the other hand, compound 8 showed little selectivity against COX-2 while compound 10 showed good selectivity against COX-1 only. Structure activity relationship has been discussed and the results were confirmed by molecular docking calculations.
KW - Anti-inflammatory activity
KW - Antipyrine
KW - COX-1
KW - COX-2
KW - Molecular modeling
KW - Pyrazolone derivatives
KW - Synthesis
UR - http://www.scopus.com/inward/record.url?scp=85042639287&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2018.01.043
DO - 10.1016/j.bmcl.2018.01.043
M3 - Article
AN - SCOPUS:85042639287
SN - 0960-894X
VL - 28
SP - 952
EP - 957
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 5
ER -