TitleNovel Series of Methyl 3-(Substituted Benzoyl)-7-Substituted-2-Phenylindolizine-1-Carboxylates as Promising Anti-Inflammatory Agents: Molecular Modeling Studies.
Publication TypeJournal Article
Year of Publication2019
AuthorsVenugopala KN, Al-Attraqchi OHA, Tratrat C, Nayak SK, Morsy MA, Aldhubiab BE, Attimarad M, Nair AB, Sreeharsha N, Venugopala R, Haroun M, Girish MB, Chandrashekharappa S, Alwassil OI, Odhav B
Date Published2019 Oct 28

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 was identified as the most active compound of the series with an IC of 6.71 M, which is comparable to the IC 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.

Alternate JournalBiomolecules
PubMed ID31661893
PubMed Central IDPMC6920857
Grant List17122011 / / Deanship of Scientific Research, King Faisal University /