Artocarpanone from Artocarpus heterophyllus heartwoods attenuates quorum sensing-regulated virulence against Pseudomonas aeruginosa and its molecular docking study

Antibiotic resistance is one of the major threats to global health. Pseudomonas aeruginosa (P. aeruginosa) is a major pathogen in nosocomial infections that has been prioritized for new antibiotic development due to its ability to rapidly develop resistance. P. aeruginosa regulates its pathogenicity, virulence, and even resistance to antibiotics via a cell-to-cell communication system called quorum sensing (QS). Artocarpanone is flavonoid compound isolated from Artocarpus heterophyllus heartwood. This compound possessed antibacterial activity against pathogenic bacteria, thus this study was undertaken to determine the effectiveness artocarpanone as a quorum sensing inhibitor agent in P. aeruginosa. Quorum sensing activity was assessed by conducting several assays, including biofilm formation, and virulence factor production assay. The molecular docking was also investigated. Artocarpanone exhibited strong antibacterial activity against P. aeruginosa with MIC and MBC values of 15.6 and 31.25 µg/mL. This compound at 2 MIC and MIC significantly inhibited the formation of biofilm along with established biofilm in P. aeruginosa. Artocarpanone reduced pyocyanin and pyoverdine production up to 16-fold in P. aeruginosa. This compound at 31.25 µg/mL also demonstrated strong activity in inhibiting protease production in tested bacteria. In the case of in silico study, Artocarpanone has hydrogen bonding interaction with an important amino acid residue i.e. Thr75 with binding free energy of -8.56 kcal/mol. It may cause that this compound become new potential to inhibit quorum sensing and virulence factor production. The result of this study provides the insight the potency of artocarpanone that can be used as alternative compound to overcome infectious problem.