Stilbenoids have been considered as an alternative phytotherapeutic treatment against methicillin-resistant Staphylococcus aureus (MRSA) infection. The combined effect of ε-viniferin and johorenol A with the standard antibiotics, vancomycin and linezolid, was assessed against MRSA ATCC 33591 and HUKM clinical isolate. The minimum inhibitory concentration (MIC) value of the individual tested compounds and the fractional inhibitory concentration index (FICI) value of the combined agents were, respectively, determined using microbroth dilution test and microdilution checkerboard (MDC) method. Only synergistic outcome from checkerboard test will be substantiated for its rate of bacterial killing using time-kill assay. The MIC value of ε -viniferin against ATCC 33591 and johorenol A against both strains was 0.05 mg/mL whereas HUKM strain was susceptible to 0.1 mg/mL of ε-viniferin. MDC study showed that only combination between ε-viniferin and vancomycin was synergistic against ATCC 33591 (FICI 0.25) and HUKM (FICI 0.19). All the other combinations (ε-viniferin-linezolid, johorenol A-vancomycin, and johorenol A-linezolid) were either indifferent or additive against both strains. However, despite the FICI value showing synergistic effect for ε-viniferin-vancomycin, TKA analysis displayed antagonistic interaction with bacteriostatic action against both strains. As conclusion, ε-viniferin can be considered as a bacteriostatic stilbenoid as it antagonized the bactericidal activity of vancomycin. These findings therefore disputed previous report that ε-viniferin acted in synergism with vancomycin but revealed that it targets similar site in close proximity to vancomycin's action, possibly at the bacterial membrane protein. Hence, this combination has a huge potential to be further studied and developed as an alternative treatment in combating MRSA in future.
Previously, a series of aurones bearing amine and carbamate functionalities was synthesized and evaluated for their cholinesterase inhibitory activity and drug-like attributes. In the present study, these aurones were evaluated for their multi-targeting properties in two Alzheimer's disease (AD)-related activities namely, monoamine oxidase (MAO) and amyloid-beta (Aβ) inhibition. Evaluation of the aurones for MAO inhibitory activity disclosed several potent selective inhibitors of MAO-B, particularly those with 6-methoxyl group attached at ring A. Of the different amine moieties attached as side chains, pyrrolidine-bearing aurones were prominent as represented by 2-2, the most potent inhibitor. Evaluation on the Aβ aggregation inhibition identified 4-3 as the best inhibitor with a percentage inhibition comparable to that of a known Aβ inhibitor curcumin. Examination on the neuroprotective ability of the more drug-like aurone 4-3 in two Caenorhabditis elegans neurodegeneration models showed 4-3 to protect the nematodes against both Aβ- and 6-hydroxydopamine-induced toxicities. These new activities further support 4-3 as a promising lead to develop the aurones as potential multipotent agents for neurodegenerative diseases.