Synthesis and in silico studies of some new pyrrolidine derivatives and their biological evaluation for analgesic and anti-inflammatory activity

Abstract

An array of commercially viable intermediate molecules necessary for the synthesis of a variety of bioactive molecules are chemically synthesized by pyrrolidine and its derivatives, which play a significant role in drug design and development process. The aim of the present research work was to explore the synthesis of some new pyrrolidine derivatives and to perform their in silico studies and finally evaluation of analgesic and anti-inflammatory activity. The purpose of this study was to synthesis new pyrrolidine derivatives, examine how they affected the COX-1 and COX-2 enzymes computationally, and to screen their in vivo analgesic and anti-inflammatory activity on laboratory animals. The new pyrrolidine derivatives were synthesized by condensing N-(3-acetylphenyl)-2-(pyrrolidin-1-yl)acetamide with substituted aniline in ethanol in the presence of catalytic amounts of glacial acetic acid. The structures of novel pyrrolidine derivatives were characterised using IR, NMR, and mass spectroscopy. Several molecular properties of the newly synthesized derivatives were calculated in order to evaluate the nature of the drug-like candidate. A specific reference cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme was used to dock the newly synthesized pyrrolidine derivatives. From the observed data, it was noted that amongst all newly synthesized compounds, A-1 and A-4 exhibited the highest anti-inflammatory and analgesic effects, respectively. On the basis of findings of present research, it was concluded that A-1 and A-4 might be utilized as a promising new lead compound for Non-Steroidal Anti-Inflammatory Drug (NSAIDs) development.