The mechanism of action underlying antibacterial activity of a diterpene quinone derivative against Staphylococcus aureus through the in vitro and in silico assays

Background: The need for new antibacterials to combat resistance is still constrained by the availability of antibacterials that are safe to use. Diterpene quinone-derived compounds are proven to have antibacterial activity. However, their mechanism of action is unknown. Objective: This study aims to determine the mechanism of antibacterial action of a diterpene quinone (6O7AR) on Staphylococcus aureus through in vitro and in silico assays. Method: MIC tests were performed using microdilution, and MBC determinations were carried out on MHA media. In vitro assays were conducted using membrane permeabilizing with Tris, Triton X-100, and ATPase-inhibiting agents with NaN3. Docking was performed on 2XCT proteins in S. aureus bacteria using AutoDock Vina. Result: The MIC and MBC results of 6O7AR were 300 μM and 2400 μM, respectively. The in vitro assay result suggested that the antimicrobial activities of 6O7AR were associated with the inhibition of ATPase function and disrupting membrane function. The docking results showed that the compound possessed good interactions with the 2XCT proteins of S. aureus. Conclusion: 6O7AR exhibited good antibacterial activity. Based on in vitro and in silico assays, the mechanism of action of this compound is related to the disruption of bacterial membrane function, and it has the potential to inhibit the ATPase enzyme and the S. aureus gyrase.