Docking studies and anti-inflammatory activity of beta-hydroxy-beta-arylpropanoic acids. 2008

Sanda P Dilber, and Silva Lj Dobric, and Zorica D Juranic, and Bojan D Markovic, and Sote M Vladimirov, and Ivan O Juranic
Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D008968 Molecular Conformation The characteristic three-dimensional shape of a molecule. Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D011422 Propionates Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure. Propanoate,Propanoic Acid,Propionate,Propanoates,Propanoic Acid Derivatives,Propanoic Acids,Propionic Acid Derivatives,Propionic Acids,Acid, Propanoic,Acids, Propanoic,Acids, Propionic,Derivatives, Propanoic Acid,Derivatives, Propionic Acid
D002351 Carrageenan A water-soluble extractive mixture of sulfated polysaccharides from RED ALGAE. Chief sources are the Irish moss CHONDRUS CRISPUS (Carrageen), and Gigartina stellata. It is used as a stabilizer, for suspending COCOA in chocolate manufacture, and to clarify BEVERAGES. Carrageenin,iota-Carrageenan,kappa-Carrageenan,lambda-Carrageenan,iota Carrageenan,kappa Carrageenan,lambda Carrageenan
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004487 Edema Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE. Dropsy,Hydrops,Anasarca
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000825 Animal Structures Organs and other anatomical structures of non-human vertebrate and invertebrate animals. Animal Organs,Animal Organ,Animal Structure,Organ, Animal,Organs, Animal,Structure, Animal,Structures, Animal
D000893 Anti-Inflammatory Agents Substances that reduce or suppress INFLAMMATION. Anti-Inflammatory Agent,Antiinflammatory Agent,Agents, Anti-Inflammatory,Agents, Antiinflammatory,Anti-Inflammatories,Antiinflammatories,Antiinflammatory Agents,Agent, Anti-Inflammatory,Agent, Antiinflammatory,Agents, Anti Inflammatory,Anti Inflammatories,Anti Inflammatory Agent,Anti Inflammatory Agents

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