Biomaterial Database

Novel Series of Methyl 3-(Substituted Benzoyl)-7-Substituted-2-Phenylindolizine-1-Carboxylates as Promising Anti-Inflammatory Agents: Molecular Modeling Studies. 2019

Katharigatta N Venugopala, and Omar H A Al-Attraqchi, and Christophe Tratrat, and Susanta K Nayak, and Mohamed A Morsy, and Bandar E Aldhubiab, and Mahesh Attimarad, and Anroop B Nair, and Nagaraja Sreeharsha, and Rashmi Venugopala, and Michelyne Haroun, and Meravanige B Girish, and Sandeep Chandrashekharappa, and Osama I Alwassil, and Bharti Odhav

Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia. kvenugopala@kfu.edu.sa.

The cyclooxygenase-2 (COX-2) enzyme is considered to be an important target for developing novel anti-inflammatory agents. Selective COX-2 inhibitors offer the advantage of lower adverse effects that are commonly associated with non-selective COX inhibitors. In this work, a novel series of methyl 3-(substituted benzoyl)-7-substituted-2-phenylindolizine-1-carboxylates was synthesized and evaluated for COX-2 inhibitory activity. Compound 4e was identified as the most active compound of the series with an IC50 of 6.71 M, which is comparable to the IC50 of indomethacin, a marketed non-steroidal anti-inflammatory drug (NSAID). Molecular modeling and crystallographic studies were conducted to further characterize the compounds and gain better understanding of the binding interactions between the compounds and the residues at the active site of the COX-2 enzyme. The pharmacokinetic properties and potential toxic effects were predicted for all the synthesized compounds, which indicated good drug-like properties. Thus, these synthesized compounds can be considered as potential lead compounds for developing effective anti-inflammatory therapeutic agents.

UI	MeSH Term	Description	Entries
D007212	Indolizines
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000894	Anti-Inflammatory Agents, Non-Steroidal	Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.	Analgesics, Anti-Inflammatory,Aspirin-Like Agent,Aspirin-Like Agents,NSAID,Non-Steroidal Anti-Inflammatory Agent,Non-Steroidal Anti-Inflammatory Agents,Nonsteroidal Anti-Inflammatory Agent,Anti Inflammatory Agents, Nonsteroidal,Antiinflammatory Agents, Non Steroidal,Antiinflammatory Agents, Nonsteroidal,NSAIDs,Nonsteroidal Anti-Inflammatory Agents,Agent, Aspirin-Like,Agent, Non-Steroidal Anti-Inflammatory,Agent, Nonsteroidal Anti-Inflammatory,Anti-Inflammatory Agent, Non-Steroidal,Anti-Inflammatory Agent, Nonsteroidal,Anti-Inflammatory Analgesics,Aspirin Like Agent,Aspirin Like Agents,Non Steroidal Anti Inflammatory Agent,Non Steroidal Anti Inflammatory Agents,Nonsteroidal Anti Inflammatory Agent,Nonsteroidal Anti Inflammatory Agents,Nonsteroidal Antiinflammatory Agents
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D051546	Cyclooxygenase 2	An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.	COX-2 Prostaglandin Synthase,Cyclo-Oxygenase II,Cyclooxygenase-2,PGHS-2,PTGS2,Prostaglandin H Synthase-2,COX 2 Prostaglandin Synthase,Cyclo Oxygenase II,Prostaglandin H Synthase 2,Prostaglandin Synthase, COX-2,Synthase, COX-2 Prostaglandin
D052246	Cyclooxygenase 2 Inhibitors	A subclass of cyclooxygenase inhibitors with specificity for CYCLOOXYGENASE-2.	COX-2 Inhibitor,COX2 Inhibitor,Coxib,Cyclooxygenase 2 Inhibitor,Cyclooxygenase-2 Inhibitor,COX-2 Inhibitors,COX2 Inhibitors,Coxibs,Cyclooxygenase-2 Inhibitors,2 Inhibitor, Cyclooxygenase,COX 2 Inhibitor,COX 2 Inhibitors,Inhibitor, COX-2,Inhibitor, COX2,Inhibitor, Cyclooxygenase 2,Inhibitor, Cyclooxygenase-2,Inhibitors, COX-2,Inhibitors, COX2,Inhibitors, Cyclooxygenase 2,Inhibitors, Cyclooxygenase-2
D062105	Molecular Docking Simulation	A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein.	Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking
D065607	Cytochrome P-450 Enzyme Inhibitors	Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 ENZYMES.	Cytochrome P-450 Inhibitors,Cytochrome P-450 Monooxygenase Inhibitors,Cytochrome P-450 Oxygenase Inhibitors,Cytochrome P-450-Dependent Monooxygenase Inhibitors,P-450 Enzyme Inhibitors,P450 Enzyme Inhibitors,Cytochrome P 450 Dependent Monooxygenase Inhibitors,Cytochrome P 450 Enzyme Inhibitors,Cytochrome P 450 Inhibitors,Cytochrome P 450 Monooxygenase Inhibitors,Cytochrome P 450 Oxygenase Inhibitors,Enzyme Inhibitors, P-450,Enzyme Inhibitors, P450,Inhibitors, Cytochrome P-450,Inhibitors, P-450 Enzyme,Inhibitors, P450 Enzyme,P 450 Enzyme Inhibitors,P-450 Inhibitors, Cytochrome