Design, Synthesis, and Biological Evaluation of a Quercetin–4-(Methylthio) phenylboronic Acid Complex with Antibacterial, Antioxidant, and Anti-Inflammatory Activities

Abstract

Quercetin is a natural occurring flavonol that has been proven to have antioxidant, antimicrobial and anti-inflammatory properties, but it is not applicable in the pharmaceutical industry because of its poor physicochemical properties. The present study was aimed to find out whether the complexation with 4-(Methylthio) phenylboronic acid (4MTPBA) could be helpful in enhancing the biological performance of quercetin. A boronate complex of quercetin with 4MTPBA was prepared by condensation at 3′4′-catechol site and further characterized by FTIR and LC-MS. Successful complex formation was achieved by the presence of characteristic B–O and B–O–C vibrations and a deprotonated molecular ion at m/z 433.06. They assessed their antibacterial activity against Salmonella typhi, Pseudomonas aeruginosa and Staphylococcus aureus by measuring zones of inhibition, MIC and MBC. The 4MTPBA–Q complex was more active than the individual quercetin and 4MTPBA against all tested bacteria with the greatest activity noted against S. aureus (24.9 mm inhibition zone, MIC 1.5625 µg/100 µL, and MBC 3.125 µg/100 µL). Antioxidant testing also showed that the complex had a higher percentage of DPPH and ABTS radicals scavenging activity of 88.9 ± 1.6% and 91.5 ± 1.7, respectively and a higher FRAP value of 356.9 ± 4.5 µmol Fe²⁺/g compared with the others. The complex showed the highest inhibitory activity towards the secretion of TNF-α, IL-6, IL-1β, PGE₂, nitrite and the expression of COX-2 in the in vitro inflammatory model, compared to the control. These results show that boronate complexation enhanced the antibacterial, antioxidant and anti-inflammatory properties of quercetin. The 4MTPBA–Q complex will have a therapeutic potential, which is supported by further in vivo and pharmacological studies.