ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Synthesis, characterization and pharmacological screening of etodolac amino acid’s mutual prodrugs

Gaurav Krishna and Kamal Shah

Institute of Pharmaceutical Research, GLA University, Mathura, India

E-mail: gk1297@gmail.com

Received: 19 June 2023  Accepted: 11 January 2024

Abstract:

Etodolac is the drug of choice for pain and inflammation associated with rheumatoid arthritis. Here, the mutual prodrugs of etodolac were synthesized using amino acid as congener. In this study, we synthesized the different amino acid methyl esters conjugated etodolac mutual prodrugs. The purpose of selecting amino acids (cysteine, glutamine and glutamic acid) is to enhance the protein synthesis and have in situ antioxidant action. The synthesized mutual prodrugs give sustained release of the parent drug moiety and in addition mask the acidic functionality of the etodolac. The synthesized prodrugs are stable in acidic environment (pH 1.2) and readily hydrolyzed in basic environment (pH 7.4). The average half-life (t^1/2) in acidic environment is ranges from 33.72 to 44.33 h and in basic medium 15.29–18.32 h. All the synthesized molecules have more analgesic and anti-inflammatory potential than etodolac. All the synthesized compounds also found to have less ulcerogenic index than parent drug. The evidence-based characterization of synthesized molecules is done by IR spectroscopy, ¹H-NMR, ¹³C-NMR and mass spectrometry.

Keywords: Etodolac; Amino acids; Mutual prodrugs; Anti-inflammatory; Analgesic; Ulcerogenic

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-024-03322-8

Chemical Papers 78 (6) 3495–3506 (2024)