Docking studies and anti-inflammatory activity of beta-hydroxy-beta-arylpropanoic acids.
The article describes a two-step synthesis of diastereomeric 3-hydroxy-2-methyl-3-(4-biphenylyl)butanoic acids. In the first step an intermediate alpha-bromo propanoic acid 1-ethoxyethyl ester was synthesized. The second step is a new modified Reformatsky reaction in presence of Zn in tetrahydrofuran (THF) at -5 to 10 degrees C between the previously synthesized intermediate and 4-acetylbiphenyl. Synthesis of the other studied beta-hydroxy-beta-arylpropanoic acids has already been reported. These beta-hydroxy-beta-arylpropanoic acids belong to the arylpropanoic acid class of compounds, structurally similar to the NSAIDs such as ibuprofen. The anti-inflammatory activity and gastric tolerability of the synthesized compounds were evaluated. Molecular docking experiments were carried out to identify potential COX-2 inhibitors among the beta-hydroxy-beta-aryl-alkanoic acids class. The results indicate that all compounds possess significant anti-inflammatory activity after oral administration and that the compounds 2-(9-(9-hydroxy-fluorenyl))-2-methylpropanoic acid (5) and 3-hydroxy-3,3-diphenyl-propanoic acid (3) possess the strongest anti-inflammatory activity, comparable to that of ibuprofen, a standard NSAID,and that none of tested substances or ibuprofen produced any significant gastric lesions.
Dilber
Sanda P
SP
Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia.
Dobric
Silva Lj
SLj
Juranic
Zorica D
ZD
Markovic
Bojan D
BD
Vladimirov
Sote M
SM
Juranic
Ivan O
IO
D000825:Animal Structures / Q000187:drug effects / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D011422:Propionates / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D000893:Anti-Inflammatory Agents; D011422:Propionates; D002351:Carrageenan; C029658:propionic acid