Synthesis and Cyclooxygenase Enzyme Inhibitory Activity of Flurbiprofen Analogues: Simple Methodology of Their Nanoemulsion Systems

• Published in: ChemistrySelect (Weinheim) Vol. 7; no. 27
• Main Authors: Taşkor Önel, Gülce, Saygılı, Nezire
• Format: Journal Article
• Language: English
• Published: 21.07.2022
• Subjects: Anti-inflammatory activity; Flurbiprofen; Ibuprofen; Nanoemulsions; NSAIDs
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202201654

Most over‐the‐counter (OTC) and prescription NSAIDs have common side effects, especially gastrointestinal problems. Flurbiprofen, is an analogue of ibuprofen, that causes side effects and discomfort. This study was to synthesize flurbiprofen analogues, determine their NSAID activity using in vitro cyclooxygenase enzyme inhibitory assays and prepare their nanoemulsions. Six new flurbiprofen derivatives were synthesized via the reaction of acyl chloride (of flurbiprofen) and β‐amino alcohol, amino acid ester (or amino dicarboxylic acid ester). The masking of the free carboxylic acid functional group of flurbiprofen lowered the acidity by nearly two‐fold. The compounds, tested for their cyclooxygenase (COX‐1 and −2) enzyme inhibitory activity, showed analogues 3 d and 3 f could be of interest due to relatively higher COX‐2 enzyme inhibition. Nanoemulsions (NEs) of flurbiprofen analogues (3 d and 3 f) were developed using high energy emulsification technique and the results showed that the optimized nanoemulsions of 3 d presented a droplet size of 225 nm, polydispersity index of 0.568, and zeta potential of +29.60 mV. Flurbiprofen, one of the most common use NSAIDs, causes significant side effects such as gastric irritation. As an interesting suggestion to this side effect, new flurbiprofen analogues were synthesized. The acidity of the analogues was reduced with the carboxylic acid functional group masked. It has been observed that COX‐2 inhibition activities were improved of the analogues. Nanoemulsion formulations of analogues were prepared with a simple method for increased bioavailability.