1Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Cyberjaya, Cyberjaya, MALAYSIA
2Department of Pharmaceutical Chemistry, Drug Discovery and Synthetic Chemistry Research Group, Kulliyyah of Pharmacy, International Islamic University Malaysia, Bandar Indera Mahkota, Kuantan, MALAYSIA
3Department of Pharmacy practice, College of Pharmacy, National University of Science and Technology, Bousher, Sultanate of OMAN
4Department of Pharmaceutics, College of Pharmacy, National University of Science and Technology, Bousher, Sultanate of OMAN
5Discipline of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, MALAYSIA
6Department of Pathology, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, MALAYSIA
7Center for Diagnostic, Therapeutics and Investigative Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, MALAYSIA
8School of Pharmacy, Faculty of Health and Medical Sciences, University of Taylor, Subang Jaya, MALAYSIA
9College of Pharmacy, Al-Bayan University, Baghdad, IRAQ
Corresponding author.
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ABSTRACT
Aim/Background
Aurone is a well-known, naturally occurring, minor flavonoid with significant biological properties. However, their low abundance in nature limits their application in the medical field. In this study, we investigated the antimicrobial and anti-inflammatory properties of a novel synthetic aurone, (Z-6-methoxy-2-(naphthalen-1-ylmethylene) benzofuran-3(2H)-one (AU-23).
Materials and Methods
AU-23 was synthesized via multistep synthesis reactions involving the oxidative cyclization of 2’-hydroxychalcones. AU-23 was tested for antibacterial, minimum inhibitory concentration and antibiofilm activity against several ATCC strains using agar well diffusion, broth-micro dilution and XTT assay methods respectively.
Results
At various concentrations, it selectively inhibited the growth of four strains (P. aeruginosa ATCC 9027, methicillin-resistant S. aureus (MRSA) ATCC 33591, methicillin-sensitive Staphylococcus aureus (MSSA) ATCC 25923 and methicillin-resistant S. aureus (MRSA) ATCC 43300). Moreover, it was observed that AU-23 had a bactericidal effect on sensitive strains of MSSA ATCC 25923 and P. aeruginosa ATCC 9027, as well as a bacteriostatic effect on MRSA ATCC 33591 and MRSA ATCC 43300. AU-23 also displayed effective antibiofilm activity against monomicrobial biofilms but not against polymicrobial biofilms. The findings of PCR study revealed that AU-23 downregulates the expression of pro-inflammatory cytokines and mediators (i.e., IL-6, IL-1β,iNOS and TNF-α), as well as crucial pattern recognition receptors (TLR4 and CD14) in LPS-stimulated RAW 264.7 cells. Molecular docking studies demonstrated that the ability of AU-23 to bind to the mouse TLR4/MD-2 complex was comparable to that of dexamethasone.
Conclusion
the results of several studies conducted, suggests that AU-23 has the potential to function as an effective dual-action agent with antimicrobial and anti-inflammatory properties.